Faculty of Medicine • Masaryk University • Brno • Czech Republic
Department of Functional Diagnostics and Rehabilitation
PROCEEDINGS
SYMPOSIUM
NONINVASIVE METHODS IN CARDIOLOGY
Edited by: F. Halberg, T. Kenner, B. Fišer, J. Siegelová
2007
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The Symposium takes place under the auspices of
Prof. PhDr. Petr Fiala, Ph.D., Rector of Masaryk University Brno
Prof. MUDr. Jan Žaloudík, CSc., Dean of Faculty of Medicine Masaryk
University Brno
SPONSORS:
Kardio-Line
Pliva – Lachema
Medicom International s.r.o.
PRO.MED.CS Praha a.s.
ISBN 978-80-7013-463-4
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CONTENS
MINIMAL REQUIREMENTS FOR DIAGNOSTIC BLOOD
PRESSURE RECORDING Kenner T............................................................................................... 5
GLOBAL CHALLENGES OF MONITORING VASCULAR VARIABILITY
AND SPACE WEATHER Halberg F.............................................................................................. 10
CHRONOMICS OF SOLAR ACTIVITY AND PERINATAL
EVENTS Cornélisen, G................................................................................................................... 28
1-DAY VERSUS 7-DAY CHAT: INDICATORS OF PHYSIOLOGICAL
VERSUS PUTATIVELY PATHOLOGICAL BLOOD PRESSURE
DYNAMICS Schwarzkopff O.......................................................................................................... 36
GEOGRAPHICALLY PROXIMAL VERSUS GLOBAL GEOMAGNETIC
REFERENCE VALUES FOR BIOLOGICAL STUDIES Cornélisen G........................................ 46
CUGINI’S MINIMAL CHANGE HYPERTENSIVE RETINOPATHY,
RESOLVED CHRONOBIOLOGICALLY WHILE DIPPING FAILS,
SUPPORT THE CONCEPT OF „PRE-HYPERTENZION“ Cornélisen G.................................... 55
CONFIDENCE INTERVALS ASSESS THE CONGRUENCE OF PERIODS
CHARACTERIZING MANY NEONATAL TRANSDISCIPLINARY NIKITYUK
CYCLES Malkova I........................................................................................................................ 62
RENAL FAILURE AND LONG-TERM EXERCISE TRAINING
- A REVIEW Kohzuki M................................................................................................................. 65
NON-INVASIVE IMAGING TECHNIQUES IN CASES OF CARDIAC
FAILURE Wolf, J-E......................................................................................................................... 68
EFFECT OF LOW VOLTAGE ELECTRICAL STIMULATION
ON ANGIOGENESIS IN RAT SKELETAL MUSCLE Nagasaka M........................................... 72
CIRCADIAN BLOOD PRESSURE VARIATION ANALYZED FROM 7-DAY
MONITORING Siegelová J............................................................................................................ 75
ANALYSIS OF BAROREFLEX FUNCTION BY MEANS OF MATHEMATICAL
MODEL Fišer B.............................................................................................................................. 90
FUNCTIONAL IMPAIRMENT AND QUALITY OF LIFE IN PATIENTS AFTER
ACUTE STROKE Tarasová M....................................................................................................... 94
WATER IMMERSION AND PHYSIOTHERAPY IN PATIENTS WITH
PARKINSON DISEASE Pospíšil P.............................................................................................. 106
PHYSIOTHERAPY AND CIRCADIAN BLOOD PRESSURE
VARIABILITY Havelková A......................................................................................................... 113
FITNESS IN MULTIPLE SCLEROSIS Konečný L.................................................................... 121
PHYSIOTHERAPY LASTING THREE MONTHS IN PATIENTS
AFTER STROKE Bártlová B....................................................................................................... 131
EXERCISE TRAINING IN OBESE PATIENTS WITH CHRONIC ISCHEMIC
HEART DISEASE Pochmonová J................................................................................................ 139
EXERCISE TRAINING IN MEN AFTER CORONARY ARTERY BYPASS
SURGERY Chludilová V.............................................................................................................. 148
FUNCTIONAL EVALUATION IN CHILDREN WITH CEREBRAL PALSY
AFTER 6-MONTHS THERAPY Drlíková L................................................................................ 156
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MINIMAL REQUIREMENTS FOR DIAGNOSTIC BLOOD PRESSURE
RECORDING
Thomas Kenner
Physiologisches Institut, Graz
Some historical considerations
The first device which has been successfully used in clinical practice for indirect blood
pressure measurement was a tonometer invented 1880 by Samuel von Basch in Vienna. A
tonometer “imitates” the palpating finger which is feeling the pulse.
One hundred and eleven years ago, in 1896, Scipione Riva Rocci, an Italian pediatrician,
published his invention, the most widely used cuff technique for blood pressure
measurement in a local Italian clinical journal.
One problem in the application of both cuff or tonometer has to do with the criterion for
the reading of pressure values. The most interesting to be mentioned are: feeling the
pulsations, hyperemia and reddening of the finger, Korotkow sounds (1905), and the
oscillatoric criterion (von Recklinghausen, 1906).
An important problem concerning all techniques of indirect blood pressure measurement is
the possible influence on the result of the dimension and of the tissue properties of the
location of the measurement.
A marked step towards the non-invasive recording of pulsatile arterial pressure was a
technique, which was developed and described by the physiologist Richard Wagner in the
1940-th. His technique of arterial unloading was a predecessor of the finger-cuff technique
by Penaz in 1969 (5).
The distension of arteries, in particular the volume pulse, can be used as an indicator of
blood pressure. As an example I have reported in 1959 an attempt to calculate the value of
the peripheral resistance and thus the pressure in the pulmonary artery from X-ray
recordings with the socalled electrokymographic technique (2). In this case it was
necessary to use a mathematical model for the interpretation of the results. As described by
Wetterer and Kenner (1968) transmission line models can be applied to determine the
frequency dependence of the pressure transformation including the so called peripheral
amplification which is due to pulse wave reflections (7). Recently O´Rourke (1996) used
the application of a transfer function to determine the aortic root pressure from tonometric
measurements of the radial pressure pulse (4).
One further important group of techniques for the indirect measurement of blood pressure
is based on the relation between arterial pressure and pulse wave velocity. From a
statistical viewpoint the pulse wave velocity is a function of age and blood pressure, as was
nicely shown by Schimmler already in 1965 (7). Since the relation between pulse wave
velocity and pressure is unique in each individual, a special calibration has to be made.
Phenomena like hysteresis have to be taken into account, which means that the result of the
measurement depends on the trend of the blood pressure variation.
The influence of gravity on the static pressure in all arteries should be mentioned when
blood pressure recording is discussed. The difference between the arterial pressure values
at the level of the head and of the kidney in an upright and a reclined position is
remarkable and may amount to about 45 mm Hg. The first observations concerning the
effect of gravity on the pulse contour have been published by J. von Kries in 1891 (6).
Raising and lowering of the arm may lead to a variation of the local pressure in the radial
artery of about 50 to 70 mmHg, depending on the length of the arm.
Conditions concerning the application of different techniques
The availability and application of non-invasive monitoring of blood pressure and the
development of specific technical devices leads to an important and interesting discussion.
This discussion has to include the answer to the following questions:
1) What are the necessary limits of precision and/or of accuracy of the measurement of
single pulses?
2) What are the constraints with respect to the limits of the duration of periods of
application of continuous recording?
The cuff technique of Riva Rocci (3)
The problem of sufficient and/or necessary accuracy and precision is a matter of discussion
related to all non-invasive techniques. The Riva-Rocci-Korotkow technique can be
considered reasonably accurate but not highly precise (3). The same is true for the
oscillometric measurement with a cuff device, which is mostly used for blood pressure
measurement by automatic devices.
6
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The “classical” techniques to record systolic and diastolic blood pressure values by
application of a brachial cuff has a low precision. However, the long term application is
nearly unlimited in that the duration depends on the tolerance of the measured person. For
the purpose of every day control and also for long duration measurement the described
properties are highly sufficient.
The tonometric technique propagated by O’Rourke (4)
It turns out that the technique developed and described by O’Rourke and coworkers which
is now available under the name Sphygmocor® is designed to attain high precision in
representing the calculated contour of the central aortic pressure pulse (4). The arterial
pulses are recorded by a hand-held tonometer at the radial artery. The central aortic
pressure contour and the corresponding pressure values are then calculated by application
of a transfer function. The high precision is important in order to permit to estimate
particular indices e.g. the amplification index. This index is assumed to be of importance
for the diagnostic purposes. With respect to an application of extended time, the pulse
recording at the radial artery by a tonometric technique limits the duration of the
measuring.
The questions concerning the reliability and the diagnostic value of the calculated pressure
contour and of the new indices appear to me to be quite a bit subjective. As discussed
extensively in the book by Wetterer and Kenner (7), there exist techniques for the quite
precise estimation of pulse transmission and reflection, which seem tome more reliable
than the new indices.
The arterial unloading technique invented by Penaz (5)
The application of the finger cuff as invented by Penaz was technically modified by several
authors and companies, and was recently improved by the company CNSystems® for
continuous pulsatile pressure recording in a device “Task force monitor”®. The main use
of this device is the recording of reactions to orthostatic load by tilt table test. However,
from a more general aspect, any device which is based on the Penaz-technique is capable
to be applied for long term experiments.
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The limits and demands of duration
Since there exists a well-known circadian variability of blood pressure (1) – and of course
many other biological variables e.g. like heart rate – it seems absurd to try a reliable
diagnostic observation from just one or a few pressure measurements taken within the
period of a physicians visit.
Normal and pathological variations of the circadian variation of blood pressure may be
important for the diagnosis of cardiovascular diseases. Therefore, a 24 hour recording of
the blood pressure appears to be the minimum demand for diagnostic purposes. Halberg (1)
demands even longer periods of recording, since some effects can only be understood if
e.g. circaseptan or even longer periods can be included in the time of observation.
In general, a compromise between the diagnostic necessity and the tolerance of the patient
must be agreed upon.
The consequence of such necessities is the fact, that the classical Riva Rocci method as
well as the improved arterial unloading techniques are superior to modern techniques of
tonometric recording and estimation of indices.
Abstract
The condition for a minimal diagnostic requirement for blood pressure recording, is the
possibility to continuously observe blood pressure during at least 24 hours.
An analysis of available non-invasive techniques for blood pressure recording shows, that
the “classical” Riva Rocci method is still superior to more modern techniques, which
restrict the time of “high accuracy recording” to less than a few minutes. Also, an
improved arterial unloading technique, as invented by Penaz, can under the given condition
also be recommended for diagnostic purposes.
Supported by MSM0021622402
Literature
(1) Cornelissen G, Halberg F (1994): Introduction to Chronobiology.
Medtronic, University of Minnesota
(2) Kenner T (1959): Über die elektrokymographische Pulskurve der Arteria pulmonalis.
9
Arch Kreislaufforschung 29: 268 - 290
(3) Kenner T, Gauer OH (1962): Untersuchungen zur Theorie der auskultatorischen
Blutdruckmessung.
Pflügers Archiv 275: 23 - 45
(4) O’Rourke MF (1996): Radical assessment of arterial pressure.
Z. Kardiol 85: Suppl 3: 134 – 135
(5) Penaz J (1969): Czech Patent 133205, Prague
(6) Von Kries J (1892): Studien zur Pulslehre.
Akademische Verlagsbuchhandlung von J.C.B. Mohr, Freiburg
(7) Wetterer E, Kenner T (1968): Dynamik des Arterienpulses.
Springer Verlag, Berlin-Heidelberg-New York
10
GLOBAL CHALLENGES OF MONITORING VASCULAR VARIABILITY AND SPACE
WEATHER
Franz Halberg1
, Germaine Cornélissen1
, Robert B. Sothern1
, Dewayne Hillman1
, George S.
Katinas1
, Ellis S. Nolley2
, Larry A. Beaty2
, Kuniaki Otsuka3
, Jarmila Siegelova4
, Frank
Greenway5
, Alok Gupta5
, Miguel Revilla6
, Anatoly Masalov7
, Elena V. Syutkina8
, Inna Malkova8
,
Sergei M. Chibisov9
, Othild Schwartzkopff1
and Earl E. Bakken10
1
University of Minnesota, Minneapolis, MN, USA
2
Phoenix Group, Institute of Electrical and Electronics Engineers, Minneapolis, MN, USA
(http://www.phoenix.tc-ieee.org; cf. http://www.sphygmochron.org/)
3
Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
4
Masaryk University, Brno, Czech Republic
5
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
6
University of Valladolid, Spain
7
Lebedev Physical Institute, Moscow, Russia
8
Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia
9
People's Friendship University of Russia, Moscow, Russia
10
North Hawaii Community Hospital Inc., Kamuela, HI, USA
Objective
In keeping with Walter Kofler's extended view of health and ecology (1), focus on time structures,
i.e., chronomes extends into (and assesses) the everyday variability of the biosphere and into its
complementary cosmos by
1. the current provision of computer-aided analyses (in exchange for the data), initially mainly of
blood pressures (BP) and heart rates (HR), not only for clinics and care providers, but above all for
the public, for self-helpers in individualized vascular health care;
2. by a service of transdisciplinary comparative analyses of a vast array of physiological and
archival time series, and by
3. using the accumulating information base for a cartography leading to an atlas with reference
standards as a requisite for diagnoses already being delivered of otherwise silent vascular
variability disorders (VVD) that may coexist as a vascular variability syndrome (VVS);
4. seeking further improvements of individuals' as well as populations' health and well-being, by
11
a. obtaining improved gender, age and ethnicity-qualified reference values for BP and HR now in
the light of decades-long (2, 3) and eventually for lifelong outcomes, and
b. obtaining refined harbingers of hard events;
c. mapping social time structures including religious proselytism (4), crime (5), terrorism (6) and
other aggression (7), all possibly related to unseen, not consciously felt magnetic and other
nonphotic as well as photic influences,
d. analyzing any triggering (as Chizhevsky put it), and/or any more consistent roles played by the
cosmos, such as pulling, driving or amplifying built-in frequencies (8) in important events among
human affairs related to the ills of society;
5. and eventually for developing countermeasures for the undesirable consequences of unseen
magnetics and other nonphotics, just as we heat and air condition against seen and felt photic and
thermal effects.
Status quo
An international BIOCOS project (on The BIOsphere and the COSmos) currently provides a
multilingual, transdisciplinarily educative and analytical worldwide service. Thereby, BIOCOS
renders a diagnosis relating to high BP more reliable (a below) and/or detects other different forms
of vascular variability disorders (VVD), including
Incidence of Vascular Variability Disorders (VVD)
in an Adult Japanese Study Population (N=297)
0
20
40
60
80
100
120
0 1 2 3 4
VVD (N irrespective of kind)
Cases(N)
VVDs considered are MESOR-Hypertension, Excessive Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above
upper 95% prediction limit of healthy peers matched by gender and age), and Deficient Heart Rate Variability (aroundthe-clock
standard deviation of HR <7.5 beats/min) obtained from 48-hour records.
36.7%
38.7%
18.5%
5.1%
1.0%
Figure 1.
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Incidence of Vascular Variability Disorders (VVD)
in an Adult Study Population (N=1177)
of both Genders (30-91 years of age)
0
100
200
300
400
500
600
700
800
0 1 2 3 4 5
VVD (N irrespective of kind)
Cases(N)
VVDs considered are MESOR-Hypertension, Excessive Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95%
prediction limit of healthy peers matched by gender and age), ecphasia (odd timing of circadian blood pressure but not heart rate
rhythm), and Deficient Heart Rate Variability (around-the-clock standard deviation of HR <7.5 beats/min) obtained from 24-hour records.
58.1%
28.4%
9.1%
3.6%
0.8% 0.0%
a. MESOR-hypertension (MHT), as a diagnosis of consistently high BP based on an account of
variability (vs. "hypertension" that may lack such a safeguard) and
b. CHAT, short for circadian hyper-amplitude-tension. Both MHT and CHAT are diagnosed on
the basis of a comparison with reference standards from gender- and age-matched peers;
c. an excessive above-threshold (of 60 mm Hg) pulse pressure (EPP);
d. a deficient heart rate variability, DHRV, and
e. ecphasia, an odd timing of the circadian rhythm of BP but not of that of HR. Irrespective of kind
of VVD, Figures 1 and 2 show how often the first 4 (a-d) VVDs coexist, and that as yet all 5
conditions have not been found to coexist in the same person in a population of 1171 people.
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Vascular Variability Disorders in a Study Population
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Caes(N)
DHRV No Yes No Yes No Yes No Yes No Yes No Yes
CHAT N o Ye s N o Ye s N o Ye s
EPP ------------ N o ------------ ------------- N o ------------- ------------ Ye s ------------
MH ------------ N o ------------ --------------------------------- Y e s ---------------------------------
Vascular variability disorders considered are
MESOR-Hypertension, Excessive Pulse Pressure
(>60 mmHg), CHAT (24h BP amplitude above
upper 95% prediction limit of healthy peers
matched by gender and age), and Deficient Heart
Rate Variability (around-the-clock standard
deviation of HR <7.5 beats/min).
Figure 2.
Vascular Variability Disorders in a Study Population
0
100
200
300
400
500
600
700
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47
Caes(N)
DHRV N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N Y
ecphasia N Y N Y N Y N Y N Y N Y N Y N Y
CHAT ----- N ----- ----- Y ----- ----- N ----- ----- Y ----- ----- N ----- ----- Y ----- ----- N ----- ----- Y -----
EPP ------------ N o ----------- ----------- Yes ------------ ----------- N o ------------ ------------ Yes ----------
MH --------------------------- N o -------------------------- --------------------------- Y e s ---------------------------
Vascular variability disorders considered are MESOR-Hypertension, Excessive
Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95%
prediction limit of healthy peers matched by gender and age), ecphasia (odd
timing of 24h BP but not HR rhythm) and Deficient Heart Rate Variability
(around-the-clock standard deviation of HR <7.5 beats/min).
Figure 3.
Figure 3 illustrates, for two populations, the N of cases in each category and Figure 4 shows a high
risk of severe vascular disease, notably when these VVDs, other than a high BP (MHT), coexist.
Coexistence then constitutes a vascular variability syndrome (VVS) with 2 or more (up to 4)
components without or usually with end organ damage. A VVD or a VVS is silent to the
conventional care provider as well as the care receiver. In the absence of MHT, VVDs can
characterize prehypertension, Figure 5 (9), and prediabetes, i.e., individuals with a fasting
hyperglycemia and an impaired morning oral glucose tolerance test (10), Figure 6a-d (11). VVDs
14
can further constitute complications for patients with MHT who are being treated for it. It is
important for "hypertensives" and validated patients with MHT alike to ascertain that the
treatment, albeit reducing or eliminating, e.g., a high BP does not do so at the cost of inducing
another VVD in BP and/or HR with a still higher risk of hard events.
If these services, offered by BIOCOS in exchange for the data analyzed, can be extended on
an appropriate scale, the accumulating transverse data could also help track biological effects of
solar variability analyzed by time-structural chronomics and may complement the lessons learned
thus far longitudinally. The discovery of transyears is a case in point, prompting a "remove and
replace" approach in physiology, Figure 7, where surgery is replaced by solar variability. We
document a. the driving by the solar wind of a spectral component (transyear with a period of ~1.3
years) in BP (by finding its partial loss when the same component is no longer detected in the solar
wind), and b. the built-in nature insofar as part of it persists, albeit with some damping, when
Figure 4.
15
Figure 4. CHAT is one of several conditions related to the variability in blood pressure (BP) and/or heart
rate (HR) that is associated with an increase in vascular disease risk. The circadian (or preferably
circaseptan profile) with too large a pulse pressure (the difference between systolic [S] BP and diastolic
[D] BP, i.e., between the heart's contraction or relaxation, or the extent of change in pressure during a
cardiac cycle) and a decreased HR variability (gauged by the standard deviation of HR) in relation to a
threshold, preferably eventually all in gender- and age-matched peers are two other risk conditions (as is
an abnormal circadian timing of BP but not of HR, not shown). Vascular disease risk is elevated in the
presence of any one of these risk factors, and is elevated further when more than a single risk factor is
present, suggesting that these abnormalities in variability of BP and HR are mostly independent and
additive. Abnormalities in the variability of blood pressure and heart rate, impossible to find in a
conventional office visit (the latter aiming at the fiction of a “true” blood pressure), can raise
cardiovascular disease risk (gauged by the occurrence of a morbid event like a stroke in the next six years)
from 4% to 100%. By comparison to subjects with acceptable blood pressure and heart rate variability, the
relative cardiovascular disease risk associated with a decreased heart rate variability (DHRV), an elevated
pulse pressure (EPP) and/or circadian hyper-amplitude-tension (CHAT) is greatly and statistically
significantly increased. These risks, silent to the person involved and to the care provider, notably the risk
of CHAT, can usually be reversed by chronobiologic self-help, also with a non-pharmacologic approach in
the absence of MESOR-hypertension.
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Figure 5
Figure 5: Subjects with minimal change retinopathy have daytime mean values of systolic blood pressure
(SBP) higher than those without retinopathy (top left); a dipping classification not only fails to resolve
prehypertension, but misleads, being normal in the presence of a minimal-change retinopathy, yet
abnormal in the absence of minimal change retinopathy (bottom). Chronobiology shows an increase in
circadian amplitude as well as MESOR, in the presence (PNS) versus the absence (TNS) of minimal
retinopathy, top right. © Halberg.
17
the solar wind loses that component. Transyears gain in applied importance, when in some
geographic locations they replace a calendar-year component in the spectrum of sudden cardiac
death (12) and suicides (13), yet overall in all available data as a whole, the photic, thermic and
social calendar dominates worldwide. Transyears again gain even more in importance when, in the
biggest MIPT Terrorism Knowledge Base (1968-2005), they dominate the spectrum in the absence
Altered Blood Pressure and Heart Rate Variability
in "Prediabetes" but not in Normoglycemia
0
1
2
3
4
5
6
Normoglycemia (N=6) Prediabetes (N=6)
Group
Incidence(Nsubjects)
Diastolic CHAT
Excessive Pulse Pressure
MESOR-Hypertension
None
(0%)
P < 0.001
(Fisher exact test)
(66.7%)
Figure 6a. Several
vascular variability
disorders characterizing
prediabetes (right half)
may be part of a
premetabolic syndrome.
Note that they are missing
in the (small sample of)
six control subjects, with
normoglycemia and an
acceptable glucose
tolerance test (left half)
(11). See also Figures 6c
and d. Data of A. Gupta.
© Halberg.
Incidence of Altered Blood Pressure Dipping*
Similar in "Prediabetes" and in Normoglycemia
0
1
2
3
4
5
6
Normoglycemia (N=6) Prediabetes (N=6)
Group
Incidence(Nsubjects)
Exessive Dipping
Non-Dipping
(50.0%)(50.0%)
* Irrespective of systolic or diastolic blood pressure
Figure 6b. A dipping
classification fails to
separate prediabetes from
normoglycemia (when a
chronobiologic approach
does so, Figure 6a) (11).
Dipping also fails in other
situations (and misled in
the case of Cugini's
prehypertension [Fig. 5]).
Data of A. Gupta. ©
Halberg.
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4) providing information about and standards for commercially available tools for manual or
automatic measurement, some ambulatorily usable monitors being available through BIOCOS in
exchange for the data to be collected, with an 80% reduction in cost by contacting
corne001@umn.edu;
5) lead up to international agreement on minimal sampling and, given appropriate time series,
minimal analysis requirements, as standards, recommended by institutions such as the IEEE and
the International Union of Physiological Sciences consulting and reporting to professional
societies of care givers;
6) making chronobiologic procedures for diagnosis (as a sphygmochron [20-23]) and therapeutics
(as a sequential test [24] and parameter comparison [25]) (preferably automatically) available on
an appropriate scale for the worldwide public, with some computer-savvy individuals, saving care
providers' time, as long as no abnormality is found and informing and educating the care provider
as need be (see 2 above). BIOCOS services have already documented the ubiquity of a VVD (26).
Although the incidence of VVDs is relatively low, the associated risk is high. Their assessment
concerns all of those now diagnosed and treated for high BP worldwide (since VVDs can silently
complicate this condition), i.e., hundreds of millions of people worldwide; incapacitation after a
21
Figure 7. Time courses of the frequency structures of the speed of the solar wind (SWS) (top) and of an
elderly man's (FH) systolic and diastolic blood pressure and heart rate, SBP, DBP and HR (rows 2-4,
respectively), examined by gliding spectral windows. Human systolic (S) blood pressure (BP) selectively
resonates with solar wind speed (SWS) (top 2 sections). No obvious resonance, only minor coincident
change in diastolic BP (DBP) or heart rate (HR) is seen (bottom 2 sections). Aeolian Rhythms* in gliding
spectra of SWS and SBP change in frequency (smoothly [A] or abruptly [B,C,D], bifurcating [D,F] and
rejoining [G], they also change in amplitude (B) (up to disappearing [C,E] and reappearing). During a
nearly 16- year span there are no consistent components with a period averaging precisely 1 year in the 3
physiologic variables, probably an effect of advancing age. While post hoc ergo propter hoc reasoning can
never be ruled out, an abrupt change on top in SWS is followed in the second row in SBP by the
disappearance of some components, suggesting that as a first demonstration, some of FH's cis- and
transyear components were driven by the SW [since they disappeared with a lag of about a transyear
following the disappearance (subtraction) of the same components from the SWS spectrum]. The
persistence of other spectral features in turn suggests endogenicity, i.e., an evolutionary acquisition of solar
transyear oscillations that may reflect solar dynamics for the past billions of years. Blood pressure and
heart rate data are from a man 70 years of age at start of around-the-clock monitoring, mostly at 30-min
intervals, with interruptions for nearly 16 years.
*FH, man, 70 years (y) of age at start of automatic half-hourly around the clock measurements for ~ 16 y
(N=2418 daily averages, total ~ 55000). Gliding spectra computed with interval = 8 y, resolution low in
time but high in frequency, increment = 1 month, trial periods from 2.5 to 0.4 y, with harmonic increment =
0.05. Darker shading corresponds to larger amplitude. When several of these broad bands disappear in the
22
SWS, at E, parts of the bands in SBP also disappear, with a lag (delay) at E’, while other parts persist.
These components are presumably built into organisms over billions of years, as persistence without
corresponding components in SWS shows, but can be driven in part by the solar wind, as their
disappearence after loss of corresponding components in SWS suggests. “Aeolian”, derived from Aeolus,
Greek god of winds, who packed the winds up, then let them loose and had them change, conceivably a
proper choice for the solar wind's pervasive role in human affairs. © Halberg.
Figure 8. The Phoenix Project of volunteering members of the Twin Cities chapter of the Institute of
Electrical and Electronics Engineers (http://www.phoenix.tc-ieee.org) is planning on developing an
inexpensive, cuffless automatic monitor of blood pressure and on implementing the concept of a website
(www.sphygmochron.org) for a service in exchange for the data that in turn are to be used for refining
methods and for monitoring psychophysiological effects of their variability in space weather. © Halberg.
massive stroke can also match any other insult. The costs are great. There is an urgent need for
prehabilitation by education, Figure 9. The same vascular and broader transdisciplinary
surveillance resolves new spectra of magnetic signatures, Figure 10, and may help clarify the
effect of solar variability upon human affairs as an endeavor complementing the monitoring in
physics introduced by Humboldt, Gauss and Sabine. Tangible current challenges and future
applications lead to the roots of social disease, to crime (5) and violence (6, 7), as well as to
sudden cardiac death (12) and suicide (13), to even broader global health and ecology.
23
Figure 9. Pre-habilitation, preferably before as well as with or after rehabilitation (for further vascular disease
prevention and more generally). By the early detection of disease risk syndromes in the individual subject,
countermeasures for primary prevention can be instituted. Such pre-habilitation in health can also complement
rehabilitation in disease and can be a major goal of health care. Pre-habilitation would complement an across-theboard
reduction of risk factors, the latter implemented by changes in lifestyle. The three entangled structures under
Chronomics stand for trends (left), chaos (right) and transdisciplinary cycles (above) that constitute the reproducible
element of the many matching time structures resolved in both the biosphere and its cosmos in the last decade,
extending the view of health and ecology (1). © Halberg.
24
a
b
c
Figure 10. Signatures of the societal and
photic-thermic year (photoperiodism) and
of nonphotic (magnetic) environmental
cycles are resolved by gliding spectra.
Therein, along an abscissa of time and an
ordinate of trial periods, shading reveals
the wobbly nature and time course of a
statistically significant spectral component
in consecutive sections (intervals) of the
time series analyzed. Photo- and
magnetoperiodisms coexist and compete in
the same clinically healthy man (RBS)
during adulthood (from 21-60 years of age,
between 1967 and 2007). Gliding spectra
computed all on daily averages with
interval = 10 years, increment = 4 months,
harmonic increment = 0.05; ordering Pvalue
from test of zero-amplitude
assumption at lightest shading is <0.01,
darker shading corresponds to larger
amplitude.
In a, in RBS's circulation, the yearly
component dominates (most for diastolic [D] blood
pressure [BP], consistently also for systolic [S] BP,
and somewhat fading with time for heart rate
[HR]). In b, a yearly component is mostly albeit
intermittently also present in self-rated vigor (V),
mood (M) and core temperature (T), but in c only to
a lesser extent in 1-minute estimation (1MTE), in
the speed of the solar wind (SWS) or the
geomagnetic index (aa). The same individual's time
structure shows wobbly aeolian (after Aeolus, ruler
of winds in ancient Greek mythology) cycles,
waxing and waning to the point of disappearing
and reappearing in amplitude, drifting, splitting,
bifurcating and rejoining in frequency, resonating
with different environmental (seen and unseen)
schedules.
Like photoperiodisms, magnetoperiodisms
have their signatures in
circadian patterns of disease. In some
geographic locations, photo- and
magnetoperiodism coexist, and in others,
magnetoperiodisms replace photoperiodisms,
e.g., in sudden cardiac death,
suicide, crime and terrorism. © Halberg.
Supported by MSM0021622402
25
References
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an "extended view" of health. Science without Borders, Transactions of the International
Academy of Science H&E, 2003/2004; 1: 27-54.
2. Müller-Bohn T, Cornélissen G, Halhuber M, Schwartzkopff O, Halberg F. CHAT und
Schlaganfall. Deutsche Apotheker Zeitung 2002; 142: 366-370 (January 24).
3. Halberg F, Schwartzkopff O, Cornélissen G, Hardeland R, Müller-Bohn T, Katinas G,
Revilla MA, Beaty L, Otsuka K, Jozsa R, Zeman M, Csernus V, Hoogerwerf WA, Nagy G,
Stebelova K, Olah A, Singh RB, Singh RK, Siegelova J, Dusek J, Fiser B, Czaplicki J,
Kumagai Y, Chibisov SM, Frolov VA. Vaskuläres Variabilitäts-Syndrom (VVS) und andere
Chronomik 2005-2007. Sitzungsberichte der Leibniz-Sozietät, in press.
4. Starbuck S, Cornélissen G, Halberg F. Is motivation influenced by geomagnetic activity?
Biomedicine & Pharmacotherapy 2002; 56 (Suppl 2): 289s-297s.
5. Halberg F, Otsuka K, Katinas G, Sonkowsky R, Regal P, Schwartzkopff O, Jozsa R, Olah A,
Zeman M, Bakken EE, Cornélissen G. A chronomic tree of life: ontogenetic and
phylogenetic 'memories' of primordial cycles - keys to ethics. Biomedicine &
Pharmacotherapy 2004; 58 (Suppl 1): S1-S11.
6. Grigoryev PYe, Vladimirskii BM. The cosmic weather affects the terrorist activity. Reports
of Taurida University, in press.
7. Halberg F, Cornélissen G, Schack B, Wendt HW, Minne H, Sothern RB, Watanabe Y,
Katinas G, Otsuka K, Bakken EE. Blood pressure self-surveillance for health also reflects
1.3-year Richardson solar wind variation: spin-off from chronomics. Biomedicine &
Pharmacotherapy 2003; 57 (Suppl 1): 58s-76s.
8. Halberg F, Cornélissen G, Sothern RB, Hillman D, Schwartzkopff O, Beaty LA, Nolley ES,
Otsuka K, Watanabe Y, Siegelova J, Fiser B, Homolka P, Singh RB. Re: Global Health and
Ecology: Individualized inferential statistical blood pressure assessment for health care and
large-scale space weather monitoring. Invited presentation for Natural cataclysms and global
problems of modern civilization, Baku, Azerbaijan, September 24-28, 2007, in press.
9. Cugini P, Cruciani F, Turri M, Regine F, Gherardi F, Petrangeli CM, Gabrieli CB. 'Minimalchange
hypertensive retinopathy' and 'arterial pre-hypertension', illustrated via ambulatory
blood-pressure monitoring in putatively normotensive subjects. International Ophthalmology
1999; 22(3): 145-149.
10. Sanchez de la Pena S, Gonzalez C, Cornélissen G, Halberg F. Blood pressure (BP), heart rate
(HR) and non-insulin-dependent diabetes mellitus (NIDDM) chronobiology. S8-06, 3rd Int
Congress on Cardiovascular Disease, Taipei, Taiwan, 26-28 Nov 2004. Int J Cardiol 2004;
97 (Suppl 2): S14.
11. Gupta AK, Greenway FL, Cornélissen G, Halberg F. Vascular variability disorders in
Louisiana, in prediabetes and in healthy women taking sex hormones. In preparation.
12. Halberg F, Cornélissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T,
Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB,
Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O,
26
Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group.
Chronobiology's progress: season's appreciations 2004-2005. Time-, frequency-, phase-,
variable-, individual-, age- and site-specific chronomics. J Applied Biomedicine 2006; 4: 1-
38. http://www.zsf.jcu.cz/vyzkum/jab/4_1/halberg.pdf
13. Cornélissen G, Halberg F. Chronomics of suicides and the solar wind. Br J Psychiatry 2006;
189: 567-568.
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Group. Hurdles to asepsis, universal literacy, and chronobiology—all to be overcome.
Neuroendocrinol Lett 2000; 21: 145-160.
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K, Watanabe Y, Kumagai Y, Syutkina EV, Kawasaki T, Uezono K, Zhao ZY, Schwartzkopff
O. Circadian Hyper-Amplitude-Tension, CHAT: a disease risk syndrome of anti-aging
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18. Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch'chen Apparates.
Berlin, med. F., Diss., 25. Nov 1880. Berlin: Schumacher; 1880. 48 p.
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pp.
20. Cornélissen G, Halberg F, Bakken EE, Singh RB, Otsuka K, Tomlinson B, Delcourt A,
Toussaint G, Bathina S, Schwartzkopff O, Wang ZR, Tarquini R, Perfetto F, Pantaleoni GC,
Jozsa R, Delmore PA, Nolley E. 100 or 30 years after Janeway or Bartter, Healthwatch helps
avoid "flying blind". Biomedicine & Pharmacotherapy 2004; 58 (Suppl 1): S69-S86.
21. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y, Halhuber
M, Müller-Bohn T, Delmore P, Siegelova J, Homolka P, Fiser B, Dusek J, Sanchez de la
Peña S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F, Schaffer E, Rhodus N,
Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and governmental challenge: 7day/24-hour
chronobiologic blood pressure and heart rate screening. Biomedical
Instrumentation & Technology 2002: Part I, 36: 89-122; Part II, 36: 183-197.
22. Halberg F, Cornélissen G, Halberg J, Schwartzkopff O. Pre-hypertensive and other
variabilities also await treatment. Am J Medicine 2007; 120: e19-e20.
doi:10.1016/j.amjmed.2006.02.045.
23. Cornélissen G, Halberg F, Otsuka K, Singh RB, Chen CH. Chronobiology predicts actual
and proxy outcomes when dipping fails. Hypertension 2007; 49: 237-239.
doi:10.1161/01.HYP.0000250392.51418.64.
24. Cornélissen G, Halberg F, Hawkins D, Otsuka K, Henke W. Individual assessment of
antihypertensive response by self-starting cumulative sums. J Medical Engineering &
Technology 1997; 21: 111-120.
27
25. Bingham C, Arbogast B, Cornélissen Guillaume G, Lee JK, Halberg F. Inferential statistical
methods for estimating and comparing cosinor parameters. Chronobiologia 1982; 9: 397-439.
26. Cornélissen G, Delcourt A, Toussaint G, Otsuka K, Watanabe Y, Siegelova J, Fiser B, Dusek
J, Homolka P, Singh RB, Kumar A, Singh RK, Sanchez S, Gonzalez C, Holley D, Sundaram
B, Zhao Z, Tomlinson B, Fok B, Zeman M, Dulkova K, Halberg F. Opportunity of detecting
pre-hypertension: worldwide data on blood pressure overswinging. Biomedicine &
Pharmacotherapy 2005; 59 (Suppl 1): S152-S157.
28
CHRONOMICS OF SOLAR ACTIVITY AND PERINATAL EVENTS
Germaine Cornélissen1
, Dana Johnson1
, Inna Malkova2
, Elena V. Syutkina2
, Anatoly Masalov3
,
Jarmila Siegelova4
, Bohumil Fiser4
, Franz Halberg1
1
University of Minnesota, Minneapolis, Minnesota, USA
2
Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia
3
Lebedev Physical Institute, Moscow, Russia
4
Masaryk University, Brno, Czech Republic
Introduction
Newborns are sensitive to their environments near and far, revealing cyclic signatures of
their cosmos in their morphology, physiology and pathology. Analyses thus far, notably when the
periods resolved are congruent in many geographic locations, suggest that there is a need to apply
a remove-and-replace approach whenever it occurs naturally, to much longer and equidistant time
series, so that the mechanisms underlying associations can be analyzed and countermeasures can
be developed for newborns' care.
Method
Chronomics, the inferential statistical approach to transdisciplinary cycles and broader time
structures - chronomes - in the biosphere and its cosmos, was applied to perinatal data against the
background of earlier studies (1, 2) with methods described elsewhere (3, 4). The database
consisted of monthly values of 18 perinatal variables, including rates of incidence of several
complications in pediatric care and anthropometric measures at birth: toxicosis, miscarriage,
anemia, respiratory infection, pyelonephritis, gestosis, premature labor, premature membrane
rupture, APGAR-1, APGAR-5, birth weight, birth height, head circumference at birth, chest
circumference at birth, small-for-gestational age (SGA), perinatal brain damage, jaundice, and
excessive weight loss.
29
Data obtained by consulting medical records were summarized as monthly rates or monthly
averages for an about 21-year span from the beginning of 1985 to the end of 2005. There were
interruptions in the recording. Data were not collected in 1987-1989 (3 years), 1992-1993 (2
years), 1996-1998 (3 years), and 2001-2002 (2 years), prompting procedures to overcome the
grave problem of artifacts from gaps (5, 6). Each section was first analyzed separately to assess
any circannual variation by the least squares fit of a 1-year cosine curve to the data, yielding
estimates of the MESOR (midline-estimating statistic of rhythms, a rhythm-adjusted mean), the
double amplitude (a measure of the predictable extent of change within a year), and the acrophase
(a measure of the timing of overall high values recurring each year). For each variable, the
circannual rhythm characteristics of each section were further summarized by population-mean
cosinor to check on the reproducibility of the circannual characteristics from one section to
another.
Least squares spectra were also obtained covering the frequency range from one cycle in 21
years to about 4 cycles per year, using a 0.2-harmonic increment. Model building was done by
nonlinear least squares, according to the following procedure: Based on earlier work, components
with periods of about 21 and 10.5 years were anticipated. Spectral peaks suggested components
with periods of about 10.5 and/or about 5 years. Plots of the data as a function of time suggested
the presence of trends for some of the variables. Accordingly, the following models were fitted: 1.
A single about 10.5-year cycle; 2. An about 10.5-year cycle and a second-order polynomial trend;
3. An about 5-year cycle and a second-order polynomial trend; 4. An about 10.5-year cycle with a
second harmonic term; 5. An about 21-year cycle; 6. An about 21-year cycle and a first-order
polynomial (or linear) trend; 7. An about 21-year cycle with a second harmonic term; 8. An about
21-year cycle with a second harmonic term and a first-order polynomial (or linear) trend; 9. An
about 21-year and about 5-year cycles. A comparison of results from the different trial models
helped determine the extent of consistency of a given component. The model selected for fitting to
the data was that associated with the smaller residual variance that included components also
identified as spectral peaks. Models consisting of components with estimated periods exceeding
30
the duration of the observation span by more than 10% were discarded. When none of the trial
models reached statistical significance, a linear or quadratic trend was fitted to the data.
Analyses were designed to also focus on the presence of any transyears, components with
periods between 1 and 2 years, with a 95% confidence interval not overlapping these limits. While
spectra included peaks in the transyear region, their validity was questioned since spurious
transyears could stem from the large gaps occurring at almost cyclic intervals in the perinatal data
series. In order to check on this possibility and in view of the presence of circadecadal cycles in
many of the perinatal variables, monthly Wolf numbers for the span from Jan 1985 to Dec 2005
were analyzed in the same fashion as the perinatal data, either using all data or only data for
months when perinatal data were available. Large spurious peaks are present not only in the
transyear range but also at frequencies as low as one cycle per 4 years. Much larger amplitudes
were seen at frequencies higher than one cycle in about 4 years for the series with gaps than for the
original equidistant series without missing values. Model building for the perinatal variables is
here limited to components with periods longer than 4 years, although new procedures were
developed to validate transyears that for several variables were more prominent than any (not
always present) yearly component.
Results
By population-mean cosinor, a circannual component was detected with statistical
significance only for gestosis (P=0.029), borderline statistical significance being reached also for
respiratory infection (P=0.078). When the circannual amplitude is expressed as a percentage of the
MESOR (to accommodate changes in overall mean associated with low-frequency components
such as the Hale and/or Schwabe cycles), or when it is equated to one (to test only for a clustering
of acrophases, irrespective of the amplitude), a circannual rhythm is detected with statistical
significance for both variables, Table 1. As seen in Table 2, many of the variables are highly intercorrelated.
Many variables share similar trends.
31
Least squares spectra indicate the presence of low-frequency trends for most variables.
Nonlinearly, results were consistent for four of the variables. An about 11-year cycle is found to
characterize respiratory infections and APGAR-1 and APGAR-5 scores, whereas premature labor
seems to follow an about 15-year cycle, possibly related to a global solar cycle (7). Premature
brain damage also seems to be primarily characterized by a Schwabe cycle. A Hale or Schwabe
cycle could not be validated nonlinearly for four other variables. A linear trend best describes
miscarriage, gestosis, and SGA, whereas a second-order polynomial is found to characterize
jaundice. Based on a trial model consisting of an about 10.5-year cycle and its second harmonic,
the Schwabe cycle is validated nonlinearly for 6 of the 54 variables, with estimated periods
varying between 10.23 and 11.59 years. An about 9.3-year component is also found for premature
membrane rupture using a model consisting only of the Schwabe cycle. Table 3 illustrates the main
positive nonlinear results for some of the variables and shows the great uncertainties involved.
Some results are in keeping with earlier work. About 10- and 20-year cycles also
characterized neonatal anthropometric measures in data from Nikityuk in Moscow and in
Kazakstan, and in data from Denmark and from Minnesota, as reported elsewhere (2).
References
1. Nikityuk BA, Alpatov AM. Secular trend in human growth and development, and solar
activity cycles. Studies in Human Ecology 1984; 5: 51-70.
2. Halberg F, Cornélissen G, Otsuka K, Syutkina EV, Masalov A, Breus T, Viduetsky A, Grafe
A, Schwartzkopff O. Chronoastrobiology: neonatal numerical counterparts to Schwabe's 10.5
and Hale’s 21-year sunspot cycles. In memoriam Boris A. Nikityuk. Int J Prenat Perinat
Psychol Med 2001; 13: 257-280.
3. Cornélissen G, Halberg F. Chronomedicine. In: Armitage P, Colton T, editors. Encyclopedia
of Biostatistics, 2nd ed. Chichester, UK: John Wiley & Sons Ltd; 2005. p. 796-812.
4. Refinetti R, Cornélissen G, Halberg F. Procedures for numerical analysis of circadian
rhythms. Biological Rhythm Research 2007; 38 (4): 275-325.
http://dx.doi.org/10.1080/09291010600903692
5. Halberg F, Cornélissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T,
Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB,
32
Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O,
Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group.
Chronobiology's progress: season's appreciations 2004-2005. Time-, frequency-, phase-,
variable-, individual-, age- and site-specific chronomics. J Applied Biomedicine 2006; 4: 1-
38. http://www.zsf.jcu.cz/vyzkum/jab/4_1/halberg.pdf
6. Halberg F, Cornélissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T,
Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB,
Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O,
Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group.
Chronobiology's progress: Part II, chronomics for an immediately applicable biomedicine. J
Applied Biomedicine 2006; 4: 73-86. http://www.zsf.jcu.cz/vyzkum/jab/4_2/halberg2.pdf
7. Markov VI, Sivaraman KR. New results concerning the global solar cycle. Solar Phys 1989;
123: 367-380.
Supported by MSM0021622402
33
Table 1: Circannual variation of several perinatal variables*
P.R. P MESOR + C.I. Amplitude (95% C.I.) Acrophase (95% C.I.)
Amplitude: Original units
1 Toxicosis 16.8 0.153 0.328 0.099 0.044 ( , ) -236 ( , )
2 Miscarriage 9.8 0.320 0.296 0.149 0.028 ( , ) -203 ( , )
3 Anemia 17.0 0.827 0.279 0.234 0.013 ( , ) -343 ( , )
4 RespInfectio 28.6 0.078 0.191 0.073 0.043 ( , ) -154 ( , )
5 Pyelonephrit 12.2 0.700 0.093 0.037 0.009 ( , ) -15 ( , )
6 Gestosis 14.8 0.029 0.199 0.048 0.028 (0.009, 0.047) -68 (-354, -110)
7 PrematureLab 9.2 0.830 0.239 0.054 0.006 ( , ) -93 ( , )
8 PremMRupt 6.2 0.946 0.493 0.084 0.002 ( , ) -197 ( , )
9 APGAR-1 6.0 0.857 7.324 0.219 0.028 ( , ) -83 ( , )
10 APGAR-5 8.8 0.910 8.280 0.322 0.007 ( , ) -208 ( , )
11 BW 12.6 0.230 3402.8 46.27 20.88 ( , ) -251 ( , )
12 Ht 9.4 0.593 51.06 0.693 0.105 ( , ) -239 ( , )
13 HC 10.4 0.307 34.75 1.013 0.056 ( , ) -82 ( , )
14 CC 8.2 0.670 34.19 0.625 0.039 ( , ) -66 ( , )
15 SGA 7.6 0.574 0.138 0.047 0.007 ( , ) -136 ( , )
16 PerinBrnDama 16.0 0.772 0.372 0.157 0.013 ( , ) -150 ( , )
17 Jaundice 17.8 0.334 0.461 0.159 0.041 ( , ) -355 ( , )
18 ExcessWtLoss 19.2 0.246 0.149 0.026 0.043 ( , ) -204 ( , )
Amplitude: Percentage of MESOR
19 Toxicosis 16.8 0.136 0.328 0.099 14.010 ( , ) -231 ( , )
20 Miscarriage 9.8 0.262 0.296 0.149 8.969 ( , ) -215 ( , )
21 Anemia 17.0 0.436 0.279 0.234 11.241 ( , ) -346 ( , )
22 RespInfectio 28.6 0.045 0.191 0.073 20.850 (9.581,32.118) -168 (-110, -232)
23 Pyelonephrit 12.2 0.911 0.093 0.037 5.806 ( , ) -10 ( , )
24 Gestosis 14.8 0.028 0.199 0.048 13.756 (7.529,19.983) -59 (-356, -116)
25 PrematureLab 9.2 0.796 0.239 0.054 3.619 ( , ) -63 ( , )
26 PremMRupt 6.2 0.984 0.493 0.084 0.286 ( , ) -180 ( , )
27 APGAR-1 6.0 0.850 7.324 0.219 0.393 ( , ) -84 ( , )
28 APGAR-5 8.8 0.891 8.280 0.322 0.087 ( , ) -208 ( , )
29 BW 12.6 0.232 3402.8 46.27 0.614 ( , ) -251 ( , )
30 Ht 9.4 0.591 51.06 0.693 0.207 ( , ) -240 ( , )
31 HC 10.4 0.308 34.75 1.013 0.164 ( , ) -81 ( , )
32 CC 8.2 0.667 34.19 0.625 0.117 ( , ) -68 ( , )
33 SGA 7.6 0.708 0.138 0.047 3.740 ( , ) -116 ( , )
34 PerinBrnDama 16.0 0.875 0.372 0.157 2.296 ( , ) -152 ( , )
35 Jaundice 17.8 0.343 0.461 0.159 7.800 ( , ) -358 ( , )
36 ExcessWtLoss 19.2 0.228 0.149 0.026 29.136 ( , ) -208 ( , )
Amplitude: Equal to one
37 Toxicosis 16.8 0.564 0.328 0.099 0.519 ( , ) -222 ( , )
38 Miscarriage 9.8 0.401 0.296 0.149 0.468 ( , ) -196 ( , )
39 Anemia 17.0 0.549 0.279 0.234 0.466 ( , ) -354 ( , )
40 RespInfectio 28.6 0.037 0.191 0.073 0.727 (0.276, 1.179) -157 (-115, -224)
41 Pyelonephrit 12.2 0.862 0.093 0.037 0.255 ( , ) -46 ( , )
42 Gestosis 14.8 0.010 0.199 0.048 0.792 (0.435, 1.150) -68 ( -11, -105)
43 PrematureLab 9.2 0.818 0.239 0.054 0.314 ( , ) -51 ( , )
44 PremMRupt 6.2 0.943 0.493 0.084 0.137 ( , ) -131 ( , )
45 APGAR-1 6.0 0.921 7.324 0.219 0.185 ( , ) -50 ( , )
46 APGAR-5 8.8 0.837 8.280 0.322 0.274 ( , ) -263 ( , )
47 BW 12.6 0.811 3402.8 46.27 0.259 ( , ) -257 ( , )
48 Ht 9.4 0.807 51.06 0.693 0.247 ( , ) -258 ( , )
49 HC 10.4 0.359 34.75 1.013 0.352 ( , ) -64 ( , )
50 CC 8.2 0.876 34.19 0.625 0.212 ( , ) -21 ( , )
51 SGA 7.6 0.999 0.138 0.047 0.019 ( , ) -38 ( , )
52 PerinBrnDama 16.0 0.799 0.372 0.157 0.277 ( , ) -110 ( , )
53 Jaundice 17.8 0.521 0.461 0.159 0.534 ( , ) 0 ( , )
54 ExcessWtLoss 19.2 0.057 0.149 0.026 0.702 ( , ) -212 ( , )
*Note failure to detect circannual variations in most variables examined, in keeping with the lack
of a prominent peak at the trial period of a calendar year and the presence of often larger
amplitudes at prior periods corresponding to transyears.
34
Table2:Correlationmatrix*
ToxicosisMiscarriageAnemiarespInfectyelonephritGestosisPremLaboremMembRAPGAR-1APGAR-5BWHtHeadCChestCSGAatBrainDamJaundicexcessWtLos
Toxicosis1.00000
Miscarriage0.481331.00000
Anemia0.614300.565071.00000
respInfect0.258220.364270.405151.00000
yelonephrit0.335390.251050.402750.097041.00000
Gestosis-0.26682-0.33680-0.22493-0.23946-0.035811.00000
PremLabo0.03960-0.122230.048030.210500.02056-0.105611.00000
emMembR0.222990.281290.133930.02094-0.00825-0.29885-0.066641.00000
APGAR-1-0.37150-0.15137-0.284200.23473-0.11436-0.122390.06586-0.199471.00000
APGAR-50.227740.398820.335890.576230.22222-0.355890.159730.042740.617911.00000
BW-0.05104-0.13425-0.129390.08441-0.067950.043410.066950.061550.180190.068711.00000
Ht0.412190.369320.452100.474400.35414-0.299220.186140.130120.149970.609710.543881.00000
HeadC-0.61191-0.70091-0.76825-0.40195-0.371140.374840.06094-0.234730.16967-0.548730.36326-0.434051.00000
ChestC-0.52258-0.52610-0.64161-0.34209-0.404830.290320.00412-0.068320.08348-0.511450.50995-0.311040.891981.00000
SGA0.167090.370900.296570.133210.09031-0.19926-0.10768-0.07463-0.069790.21489-0.65246-0.14441-0.51185-0.530571.00000
atBrainDam0.440910.359820.543990.116030.22490-0.05377-0.143320.19893-0.56896-0.10302-0.105390.20384-0.48757-0.270840.177741.00000
Jaundice0.340310.404360.605450.299220.31778-0.102090.006540.15248-0.016920.45602-0.121740.43280-0.66002-0.633590.324180.197501.00000
xcessWtLo0.11741-0.02630-0.02462-0.06244-0.139140.008320.114530.15080-0.30262-0.217700.00851-0.186970.104440.15512-0.016880.07796-0.264531.00000
*
Pearsonproduct-momentcorrelationscoefficientsforpairedvariables.Boldindicatesstatisticallysignificantcorrelation(P<0.05).
35
Table 3: Nonlinear results with different models show Schwabe or Hale cycles putative
signatures by CIs (95% confidence intervals) overlapping the about 10.5, 15 and 21-years*
Variable Period (95% CI) Amplitude (95% CI) A-Harm 2 (95% CI)
Trial Model: Period = 21.0 years
Toxicosis 26.126 17.732 34.520 0.10 0.06 0.14
Miscarriage 37.100 11.026 63.174 0.14 0.09 0.19
Anemia 23.500 21.490 25.510 0.25 0.21 0.29
Pyelonephritis 27.233 7.345 47.122 0.04 0.01 0.07
Gestosis 30.534 0.867 60.202 0.05 0.01 0.08
Premature Labor 15.112 11.003 19.221 0.05 0.00 0.09
Premature Membrane
Rupture
21.817 13.460 30.173 0.08 0.03 0.12
APGAR-1 10.174 9.687 10.661 0.40 0.26 0.54
Head Circumference 29.397 25.286 33.509 0.96 84.00 1.07
Chest Circumference 29.415 20.127 38.703 0.59 0.44 0.75
SGA 31.231 1.097 61.365 0.04 0.01 0.07
Perinatal Brain Damage 20.277 17.577 22.976 0.17 0.11 0.23
Jaundice 38.126 8.682 67.569 0.19 0.06 0.32
Trial Model: Period = 21.0 years and 1st-order Polynomial
Toxicosis 11.470 7.248 15.692 0.05 0.00 0.12
Pyelonephritis 18.614 5.197 32.031 0.03 0.00 0.06
Premature Labor 15.375 10.158 20.592 0.05 0.00 0.09
Premature Membrane
Rupture
14.798 11.622 17.974 0.08 0.03 0.14
APGAR-1 10.556 9.847 11.266 0.39 0.26 0.53
APGAR-5 10.442 9.835 11.049 0.29 0.19 0.38
Birth Weight 12.951 9.625 16.277 51.66 0.97 102.36
Head Circumference 15.230 9.306 21.155 0.32 0.18 0.46
Chest Circumference 14.251 11.684 16.817 0.32 0.12 0.53
Perinatal Brain Damage 10.841 9.649 12.034 0.18 0.09 0.27
Trial Model: Period = 21.0 years and 2nd Hamonic Term
APGAR-1 19.920 18.877 20.964 0.15 0.05 0.24 0.40 0.25 0.55
APGAR-5 22.724 21.203 24.245 0.19 0.13 0.24 0.33 0.24 0.43
Chest Circumference 22.352 19.150 25.553 0.66 0.47 0.86 0.32 0.05 0.60
Perinatal Brain Damage 16.289 14.618 17.960 0.22 0.13 0.31 0.18 0.11 0.26
Trial Model: Period = 21.0 years and 2nd Hamonic Term and 1st-order Polynomial
Toxicosis 11.357 10.235 12.480 0.08 0.02 0.15 0.08 0.00 0.16
APGAR-1 16.828 15.209 18.446 0.41 0.26 0.56 0.39 0.24 0.54
APGAR-5 17.938 15.625 20.251 0.22 0.07 0.37 0.27 0.16 0.38
Perinatal Brain Damage 15.825 13.780 17.871 0.22 0.13 0.30 0.16 0.06 0.27
Excess Weight Loss 13.973 12.513 15.433 0.06 0.00 0.12 0.06 -0.01 0.12
*Overlap indicates no more than great uncertainties and need for more data.
Results not shown when model did not fit data:
- for period = 21.0 years, respiratory infection, APGAR-5, birth weight and height at birth, and excess weight loss;
- for period = 21.0 years and first-order polynomial, miscarriage, anemia, respiratory infection, gestosis, height at birth, SGA, jaundice and excess
weight loss;
- for period = 21.0 years and 2nd harmonic term, toxicosis, miscarriage, anemia, respiratory infection, pyelonephritis, gestosis, premature labor,
premature membrane rupture, birth weight, height at birth, head circumference, SGA, jaundice and excess weight loss;
- for period = 21.0 years, 2nd harmonic term and 1st-order polynomial: miscarriage, anemia, respiratory infection, pyelonephritis, gestosis,
premature labor, premature membrane rupture, birth weight, height at birth, head and chest circumference, SGA and jaundice
36
1-DAY VERSUS 7-DAY CHAT: INDICATORS OF PHYSIOLOGICAL VERSUS
PUTATIVELY PATHOLOGICAL BLOOD PRESSURE DYNAMICS
Othild Schwartzkopff•, Kuniaki Otsuka*, Shirley Stinson‡, Germaine Cornélissen•, Jarmila
Siegelova§, Inna Malkova¶, Elena V. Syutkina¶, Anatoly Masalov∆, Bohumil Fiser§, Franz
Halberg•
•University of Minnesota, Minneapolis, MN, USA
*Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
‡University of Alberta, Edmonton, AB, Canada
§Masaryk University, Brno, Czech Republic
¶Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia
∆Lebedev Physical Institute, Moscow, Russia
Objective
To document further beyond earlier studies (1, 2) the need for a minimal 7-day record, if
abnormalities indicating a risk of stroke and other severe illness greater than that of hypertension
(3, 4) are to be picked up and reliably diagnosed in order to be treated if they are consistent upon
further monitoring.
Method
The linear-nonlinear extended cosinor (5-7) had demonstrated on several hundred series that
the vast majority of invariably complete 7-day-long blood pressure (BP) records, the circadian
periods had a 95% confidence interval that overlapped the precise 24-hour length.
Results
Sets of hundreds of 7-day series from several continents showed great day-to-day variability.
Table 1 summarizes 3-hourly manual BP and HR measurements around the clock for 7 days. The
average for a week of 136 mm Hg can vary as daily averages between 130 and 143 mm Hg SBP.
37
The day-night ratio for DBP can indicate a dipper on 4 days, reverse dipping on 3 days and thus
nondipping as the overall result. Table 2 also reveals week-to-week variability by
chronobiologically interpreted ambulatory blood pressure measurements (C-ABPM). Figure 1
shows analyses of a record from an elderly woman (OS) who had monitored herself for years and
had no MESOR elevations, but had occasional 1-day CHAT (in 24-hour spans of course); the
CHAT was eliminated from all 7-day records when these were analyzed as a whole, Figure 2. The
contribution of outlying days' records was washed out by the fit of a fixed 2-component model (of
24-hour and 12-hour cosine curves) to the entire series, the purpose of the procedure. Thus, when
in Figure 3 all data are summarized for this MESOR-normotensive elderly woman on a daily basis,
there is 7% 1-day-CHAT, while on a weekly analysis, there is 0% 7-day CHAT in Figure 4: one
more reason to insist on a minimal 7-day record, so that no false diagnosis is likely to be given to
those who have only transient CHAT while an individual who has frequent CHAT is recognized,
further investigated and treated if necessary.
The difference between 1-day and 7-day CHAT is further apparent when a batch of 15 series
was picked to compare the daily incidence of CHAT with the weekly incidence, when the weekly
summary was again computed by the fit by cosinor of a 2-component model of a 24- and a 12-hour
cosine curve. When the 7-day record was analyzed on a daily basis, Figure 5 shows that of the 15
elderly individuals, only 3 had no day without CHAT and none had CHAT on each day. Twelve
persons (80%) had one or more days with CHAT, which is a physiologically encountered
condition. One of them had 5 single-day analyses documenting 1-day CHAT, but no overall
excessive circadian amplitude, no 7-day CHAT. Only 3 of the 15 elderly subjects, 20% rather than
80%, had a diagnosis of 7-day CHAT. A diagnosis of 7-day CHAT or of less frequent CHAT
should prompt further monitoring. The lack of 1-day as well as 7-day CHAT, while reassuring in
the absence of other variability disorders, does not dispense with further monitoring, e.g., at yearly
intervals, until unobtrusive, generally affordable instrumentation becomes available so that nobody
ever flies blind (8), keeping the week-to-week variability in mind.
Supported by MSM0021622402
38
References
1. Schaffer E, Cornélissen G, Rhodus N, Halhuber M, Watanabe Y, Halberg F. Outcomes of
chronobiologically normotensive dental patients: a 7-year follow-up. JADA 2001; 132: 891-
899.
2. Halberg F, Cornélissen G, Sothern RB, Hillman D, Schwartzkopff O, Beaty LA, Nolley ES,
Otsuka K, Watanabe Y, Siegelova J, Homolka P, Fiser B, Singh RB. Re: Global Health and
Ecology: Individualized inferential statistical blood pressure assessment for health care and
large-scale space weather monitoring. Invited presentation for Natural cataclysms and global
problems of modern civilization, Baku, Azerbaijan, September 24-28, 2007, in press.
3. Otsuka K, Cornélissen G, Halberg F. Predictive value of blood pressure dipping and
swinging with regard to vascular disease risk. Clinical Drug Investigation 1996; 11: 20-31.
4. Halberg F, Cornélissen G, International Womb-to-Tomb Chronome Initiative Group:
Resolution from a meeting of the International Society for Research on Civilization Diseases
and the Environment (New SIRMCE Confederation), Brussels, Belgium, March 17-18, 1995:
Fairy tale or reality ? Medtronic Chronobiology Seminar #8, April 1995, 12 pp. text, 18
figures. URL http://www.msi.umn.edu/~halberg/
5. Halberg F. Chronobiology: methodological problems. Acta med rom 1980; 18: 399-440.
6. Cornélissen G, Halberg F. Chronomedicine. In: Armitage P, Colton T, editors. Encyclopedia
of Biostatistics, 2nd ed. Chichester, UK: John Wiley & Sons Ltd; 2005. p. 796-812.
7. Refinetti R, Cornélissen G, Halberg F. Procedures for numerical analysis of circadian
rhythms. Biological Rhythm Research 2007; 38 (4): 275-325.
http://dx.doi.org/10.1080/09291010600903692.
8. Fossel M. Editor's Note [to Halberg F, Cornélissen G, Halberg J, Fink H, Chen C-H, Otsuka
K, Watanabe Y, Kumagai Y, Syutkina EV, Kawasaki T, Uezono K, Zhao ZY, Schwartzkopff
O. Circadian Hyper-Amplitude-Tension, CHAT: a disease risk syndrome of anti-aging
medicine. J Anti-Aging Med 1998; 1: 239-259]. J Anti-Aging Med 1998; 1: 239.
39
DateSBPDBPHR
Jun07M2AφM2AφM2Aφ
134.62.4915:3676.17.9914:1079.617.6915:13
MeanSDDNRMeanSDDNRmeanSDDNR
136.329.681.72%76.567.217.22%79.609.1916.66%
SMSSti25:22-23Fri/Sat137.278.53-2.9177.735.42-7.7281.3511.1412.26
06/22-23-24Sat/Sun135.189.855.3375.647.7914.1581.009.1019.51
29/200724-25Sun/Mon132.149.477.1974.148.2414.5074.577.4418.10
25-26Mon/Tue142.7810.07-10.8679.568.11-13.2078.6710.5419.70
26-27Tue/Wed135.888.014.4276.756.6714.3382.756.9210.27
27-28Wed/Thu142.006.22-0.9279.756.34-0.2579.678.1319.83
28-29Thu/Fri130.1010.35-0.1973.006.2212.3381.2010.4515.39
*C:chronobiologicallycollectedandinterpretedBPandHRmeasurement;MBPM:manualbloodpressuremeasurement
(aboutevery3hoursaroundtheclockfor7days)
M:MESOR(midline-estimatingstatisticofrhythm),arhythm-adjustedmean,thatmaydifferslightlyfromarithmeticmeanlistedbelow
2A:doublecircadianamplitude:extentofpredictablechangewithinaday
φ:circadianacrophase:ameasureoftimingofoverallhighvaluesoccurringeachday,expressedinhr:min
SD:standarddeviation;DNR:day-nightratio
UnderliningindicatesabnormalityinDNRofSBPandDBP
Table1:Chronobiologicallyinterpreted,systematicmanual7-day/24-hmonitoringofsystolic(S)and
diastolic(D)bloodpressure(BP)andheartrate(HR)(C-MBPM)revealsday-to-dayvariability:SS,F,72y
40
DateSystolicbloodpressure(mmHg)Diastolicbloodpressure(mmHg)Heartrate(beats/min)
SeriesMay2007M±SEA±SEφ±SEM±SEA±SEφ±SEM±SEA±SEφ±SE
I07Mon133.7±3.68.18±5.18-219±3572.9±2.29.34±3.18-234±1958.4±2.13.39±2.87-294±52
08Tue123.4±3.516.70±5.06-217±1770.5±2.512.59±3.57-216±1656.9±1.74.63±2.45-19±29
09Wed139.3±3.129.01±4.49-233±978.5±1.818.85±2.60-234±862.8±2.53.81±3.49-159±52
10Thu117.4±3.26.45±4.64-197±4065.5±1.95.85±2.79-205±2655.9±1.26.25±1.65-8±15
11Fri125.6±3.113.30±4.47-257±1968.4±2.413.21±3.50-238±1454.0±1.26.65±1.77-27±15
12Sat123.3±3.47.74±4.44-273±3763.9±2.310.85±2.93-309±1953.7±1.57.32±2.26-10±15
13Sun116.9±2.78.62±4.01-244±2566.8±2.16.79±3.06-252±2455.3±1.15.20±1.55-348±18
Rangeofvariability116.9–139.36.45–29.01-197–-27363.9–78.55.85–18.85-205–-30953.7–62.83.39–7.32-294–-27(&"-159")
II22Tue123.7±2.611.23±3.70-266±1972.1±2.19.29±2.99-273±1860.1±1.410.55±1.99-42±10
23Wed124.9±3.517.69±4.99-190±1667.9±2.510.91±3.56-181±1861.5±2.03.35±2.83-12±47
24Thu131.5±2.912.20±4.14-235±1972.4±2.29.84±3.17-226±1862.3±2.212.90±3.07-45±14
25Fri128.3±3.618.55±5.10-219±1571.7±2.416.27±3.48-220±1252.8±0.96.05±1.23-32±12
26Sat126.9±2.315.98±3.22-255±1170.2±2.313.37±3.24-247±1454.5±1.24.37±1.78-15±23
27Sun124.0±2.213.02±3.10-197±1467.6±1.88.40±2.55-199±1757.5±1.76.16±2.36-5±22
28Mon126.1±2.913.81±4.15-220±1771.0±2.610.41±3.63-225±2052.3±1.27.46±1.68-15±13
Rangeofvariability123.7–131.511.23–18.55-190–-26667.6–72.48.40–16.27-181–-27352.3–62.33.35–12.90-5–-45
M:MESOR(midline-estimatingstatisticofrhythm),arhythm-adjustedmean,thatmaydifferslightlyfromarithmeticmean
A:circadianamplitude:halftheextentofpredictablechangewithinaday
φ:circadianacrophase:ameasureoftimingofoverallhighvaluesoccurringeachday,expressedin(negative)degrees,with360Þ≡24h,0Þ=00:00
SE:standarderror
Dailyspanscovermidnighttomidnight
Table2:Day-to-dayvariabilitycandifferfromweektoweek(Ivs.II):FH,M,88y
41
Figure1
0
20
40
60
80
100
120
140
160
180
200
Time(calendaryears)
CONSECUTIVEAVERAGES(above)andCIRCADIANSWINGS(below)
ofSYSTOLICBLOODPRESSURE(SBP)DURING~2YEARS
ALTERNATEBETWEENMOSTLYACCEPTABLEandRARELYUNACCEPTABLE*
*Resultsfromnon-overlapping24-hintervalsinserialsectionsonhalf-hourlyaroundtheclockdata;OS
(F,81-82y)onatenololtreatment.**MH=MESOR-Hypertension,CHAT=CircadianHyper-Amplitude
Tension.
MH**
Yes
No
CHAT
Yes
No
Upper95%predictionlimits
ofgender-,age-andgeography-matched
healthypeers
MESORbasedon
24-hourintervals
DoubleCIRCADIANAmplitude
basedon24-hourintervals
20042005
42
Figure2
0
20
40
60
80
100
120
140
160
180
200
Time(calendaryears)
CONSECUTIVEAVERAGES(above)andCIRCADIANSWINGS(below)
ofSYSTOLICBLOODPRESSURE(SBP)DURING~2YEARS
AREALLACCEPTABLE*
*Resultsfromnon-overlapping7-dayintervalsinserialsectionsonhalf-hourlyaroundtheclockdata;OS
(F,81-82y)onatenololtreatment.**MH=MESOR-Hypertension,CHAT=CircadianHyper-Amplitude
Tension.When1-dayintervalsareused,occasionalunacceptableresultsoccur.
MH**
Yes
No
CHAT
Yes
No
Upper95%predictionlimits
ofgender-,age-andgeography-matched
healthypeers
MESORbasedon
168-hourintervals
DoubleCIRCADIANAmplitude
basedon168-hourintervals
20042005
43
Figure 3
0
20
40
60
80
100
100 110 120 130 140 150 160 170
SBP-MESOR (mm Hg)
NORMOTENSION
CIRCADIAN
HYPER-AMPLITUDE
TENSION (CHAT)
MESOR-
HYPERTENSION
CHAT
+
MESOR-
HYPERTENSION
93.0 %
7.0 % 0.0 %
0.0 %
0.0 %
0.0 %
* OS (F, 81-82 y in 2005-2006) on (25 mg/day, on awakening) atenolol
treatment.
Results from non-overlapping (fractionated) serial sections over daily
intervals on half-hourly around-the-clock measurements. Daily records with
fewer than 36 values discarded.
7.0 %
93.0 %
100.0 % 0.0 % 0.0 %
24h-BASED CHAT/MESOR-HYPERTENSION INDEX 7.0/0.0
MESOR (M) and DOUBLE AMPLITUDE (2A)
OF SYSTOLIC BLOOD PRESSURE (SBP)*
44
Figure 4
0
10
20
30
40
50
100 110 120 130 140 150 160 170
SBP-MESOR (mm Hg)
NORMOTENSION
CIRCADIAN
HYPER-AMPLITUDE
TENSION (CHAT)
MESOR-
HYPERTENSION
CHAT
+
MESOR-
HYPERTENSION
100 %
0.0 %
0.0 %
0.0 %
100 %
100.0 % 0.0 % 0.0 %
168h-BASED CHAT/MESOR-HYPERTENSION INDEX 0.0/0.0
MESOR (M) and DOUBLE AMPLITUDE (2A)
OF SYSTOLIC BLOOD PRESSURE (SBP)*
* OS (F, 81-82 y in 2005-2006) on (25 mg/day, on awakening) atenolol
treatment.
Results from non-overlapping (fractionated) serial sections over weekly
intervals on half-hourly around-the-clock measurements analyzed. Weekly
records with fewer than 224 values discarded.
0.0 % 0.0 %
0.0 %
45
Figure5
46
GEOGRAPHICALLY PROXIMAL VERSUS GLOBAL GEOMAGNETIC REFERENCE
VALUES FOR BIOLOGICAL STUDIES
Germaine Cornélissen1
, Waldemar Ulmer2
, Inna Malkova3
, Elena V. Syutkina3
, Anatoly Masalov4
,
Rüdiger Hardeland5
, Hans-Joachim Linthe6
, Armin Grafe6
, Kuniaki Otsuka7
, Jarmila Siegelova8
,
Bohumil Fiser8
, Franz Halberg1
1
Halberg Chronobiology Center, University of Minnesota, Minneapolis, Minnesota, USA
2
VARIAN International, Zug, Switzerland
3
Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia
4
Lebedev Physical Institute, Moscow, Russia
5
University of Göttingen, Germany
6
GeoForschungsZentrum Potsdam, Niemegk, Germany
7
Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
8
Masaryk University, Brno, Czech Republic
Background
Geomagnetic activity during spans matching two experiments (actually surveys) in
Göttingen on tumor cell growth is here analyzed. The spectrum of the planetary geomagnetic
disturbance index Kp is compared with that of the local geomagnetic disturbance index K from
Niemegk (the closest recording station identified). One protocol specified cells cultured at pH 6.9
over 44 days in 1997, another followed a few days later at pH 7.3 also over 44 days (1). During
each span, four kinds of mammalian tumor cells were grown (B14, C3H, G9L and L1210). After
detrending the growth curve, two major components were identified with periods of 7 days and 24
hours, both synchronized to the social week and day, respectively. The circaseptan amplitude was
much larger than the circadian amplitude for each culture at each pH. A third spectral component
with a period slightly longer than a month was also found. Of primary interest were the findings
(on cells kept mostly in continuous darkness) that the circaseptan component not only had an
47
amplitude much larger than that of a circadian rhythm but also that the rhythms were 1-week and
24-hour synchronized. It seemed reasonable to seek similar precise components in the
environment, notably since near-weekly but not precisely 1-week-long cycles had been found
earlier in the polarity of the interplanetary magnetic field (2) and in geomagnetic activity (3-5).
Materials and Methods
In order to explore whether the tumor cell cultures could have been synchronized by
magnetoperiodisms, both the planetary index Kp of geomagnetic activity and the index from
Niemegk (NGK) were analyzed during the same two 44-day spans as the two surveys on tumor
cell cultures' growth. Analyses consisted of linear-nonlinear rhythmometry by the extended
cosinor (6).
Results
As seen in Figure 1a, Kp and NGK follow a similar time course. The two indices are highly
correlated (r>0.85, P<0.001), Figure 1b. The major expected difference between the two indices is
apparent from the least squares spectra of Kp in Figures 2a-b vs. NGK in Figures 3a-b: whereas
the circadian component is not statistically significant for Kp (which is an average index from
several stations worldwide), it clearly corresponds to a major spectral peak for the local index
NGK during both study spans.
The nonlinear results are shown in Table 1. For Kp, only the circaseptan component could be
validated with statistical significance. During the first survey, the period of Kp does not differ
from 7 days as the 95% confidence interval for the period covers 7 days. During the second
survey, the circaseptan is slightly longer than 7 days. In the case of NGK, the circaseptan period
does not differ from 7 days during either survey. In addition, the circadian component is detected
with statistical significance, its period not differing from 24 hours. Whereas the circadian
amplitude is larger than the circaseptan one during the first survey, it is slightly smaller during the
second survey.
48
As compared to results on tumor cell growth, results on Kp or NGK differ in several
respects. First, the circaseptan-to-circadian amplitude ratios are quite different, with the
circaseptan considerably and invariably more prominent than the circadian in the cell cultures but
not in geomagnetic activity. Second, the slight tendency of Kp to assume a period somewhat
longer than 7 days during the second survey contrasts with the 7-day synchronized component
characterizing all four tumor cell cultures at both pH values investigated. As seen in the least
squares spectra, the 7-day component (corresponding to the vertical line at 1 cycle/week) by no
means corresponds to the tallest spectral peak in the case of Kp or NGK. Several other peaks are
observed to bracket the circaseptan component of Kp or NGK. A possible modulation of the
circaseptan component by the very prominent about 27-day variation corresponding to the solar
rotation period around its axis must be kept in mind.
Discussion
Effects of geomagnetic activity or magnetic storms are inferentially documented, acting
directly on cell division (7) and indirectly on cancer therapy (8, 9), on cardiac function (10-12) and
the endocrines (13). Associations at the population level with terrorism are also reported (14).
Conclusion
It seems possible that geomagnetics, gauged by a local index (NGK), but not on the basis of
data for the planetary index Kp, contributed to the synchronization of the tumor cell cultures at
both the circadian and circaseptan frequency. The circaseptan-to-circadian amplitude ratios in Kp
and NGK differ, however, from those found in the cell cultures investigated. We cannot suggest
that any spectral component characterizing geomagnetics was responsible for what appears to be
an unknown precise 7-day and 24-hour (societal or equipment-derived) synchronizer. Almost
certainly, however, in any biospheric study, the nearest geomagnetic disturbance index, rather than
only any planetary index, should be considered, even when, in the absence of records from a
nearby station, important results are sometimes found at the planetary level (7, 14).
Supported by MSM0021622402
49
REFERENCES
1. Ulmer W, Cornélissen G, Revilla M, Siegelova J, Dusek J, Halberg F. Circadian and
circaseptan dependence of the beta-ATP peak of four different cancer cell cultures:
implications for chronoradiotherapy. Scripta medica (Brno) 2001; 74: 87-92.
2. Gonzalez ALC, Gonzalez WD. Periodicities in the interplanetary magnetic field polarity. J
Geophys Res 1987; 92: 4357-4375.
3. Halberg F, Breus TK, Cornélissen G, Bingham C, Hillman DC, Rigatuso J, Delmore P,
Bakken E, International Womb-to-Tomb Chronome Initiative Group: Chronobiology in
space. Keynote, 37th Ann. Mtg. Japan Soc. for Aerospace and Environmental Medicine,
Nagoya, Japan, November 8-9, 1991. University of Minnesota/Medtronic Chronobiology
Seminar Series, #1, December 1991, 21 pp. of text, 70 figures.
4. Roederer JG. Are magnetic storms hazardous to your health? Eos, Transactions, American
Geophysical Union 1995; 76: 441, 444-445.
5. Vladimirskii BM, Narmanskii VYa, Temuriantz NA. Global rhythmics of the solar system in
the terrestrial habitat. Biophysics 1995; 40: 731-736.
6. Halberg F. Chronobiology: methodological problems. Acta med rom 1980; 18: 399-440.
7. Halberg F, Cornélissen G, Schwartzkopff O, Katinas GS, Chibisov SM, Khalitskaya EV,
Mitsutake G, Otsuka K, Scheving LA, Bakken EE. Chronometaanalysis: magnetic storm
associated with a reduction in circadian amplitude of rhythm in corneal cell division.
Proceedings, International Conference on the Frontiers of Biomedical Science:
Chronobiology, Chengdu, China, September 24-26, 2006, p. 40-42.
8. Blank MA, Cornélissen G, Halberg F. Circasemiseptan (about half-weekly) and/or
circaseptan (about-weekly) pattern in human mitotic activity? In vivo 1995; 9: 391-394.
50
9. Blank MA, Gushchin VA, Halberg F, Portela A, Cornélissen G. X-irradiation
chronosensitivity and circadian rhythmic proliferation in healthy and sarcoma-carrying rats'
bone marrow. In vivo 1995; 9: 395-400.
10. Otsuka K, Cornélissen G, Weydahl A, Holmeslet B, Hansen TL, Shinagawa M, Kubo Y,
Nishimura Y, Omori K, Yano S, Halberg F. Geomagnetic disturbance associated with
decrease in heart rate variability in a subarctic area. Biomedicine & Pharmacotherapy 2001;
55 (Suppl 1): 51s-56s.
11. Chibisov SM, Cornélissen G, Halberg F. Magnetic storm effect on the circulation of rabbits.
Biomedicine & Pharmacotherapy 2004; 58 (Suppl 1): S15-S19.
12. Cornélissen G, Halberg F, Breus T, Syutkina EV, Baevsky R, Weydahl A, Watanabe Y,
Otsuka K, Siegelova J, Fiser B, Bakken EE. Non-photic solar associations of heart rate
variability and myocardial infarction. J Atmos Solar-Terr Phys 2002; 64: 707-720.
13. Jozsa R, Halberg F, Cornélissen G, Zeman M, Kazsaki J, Csernus V, Katinas GS, Wendt
HW, Schwartzkopff O, Stebelova K, Dulkova K, Chibisov SM, Engebretson M, Pan W,
Bubenik GA, Nagy G, Herold M, Hardeland R, Hüther G, Pöggeler B, Tarquini R, Perfetto
F, Salti R, Olah A, Csokas N, Delmore P, Otsuka K, Bakken EE, Allen J, Amory-Mazaudier
C. Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts
-- forecasts of geomagnetics. Biomedicine & Pharmacotherapy 2005; 59 (Suppl 1): S24-S30.
14. Grigoryev PYe, Vladimirskii BM. The cosmic weather affects the terrorist activity.
Conference, Scientific Notes of Taurida University, in press.
51
Figure 1: Geomagnetic Activity Index Kp and Local Niemegk K Index
During Spans Matching Two Surveys on Tumor Cell Growth
a. Similar time course of the two indices:
Experiments #1&2: pH = 6.9&7.3
0.0
2.0
4.0
6.0
8.0
10.0
12.0
29-
Aug
05-
Sep
12-
Sep
19-
Sep
26-
Sep
03-
Oct
10-
Oct
17-
Oct
24-
Oct
31-
Oct
07-
Nov
14-
Nov
21-
Nov
28-
Nov
Time (calendar date)
Kp
Experiment #1 [pH=6.9] Experiment #2 [pH=7.3]
=K+4 [NGK]
Kp
b. High correlation between the two indices:
0
2
4
6
8
10
0 2 4 6 8 10
Kp
NGK
Exp #1 [pH=6.9]
r = 0.892, P < 0.001
Exp #2 [pH=7.3]
r = 0.911, P < 0.001
52
Figure 2. Spectra of Kp:
Kp: Exp#1 (pH=6.9)
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16
Frequency (cycles per week)
Amplitude
Kp: Exp#2 (pH=7.3)
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16
Frequency (cycles per week)
Amplitude
53
Figure 3. Spectra of Niemegk K index:
NGK: Exp#1 (pH=6.9)
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16
Frequency (cycles per week)
Amplitude
NGK: Exp#2 (pH=7.3)
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16
Frequency (cycles per week)
Amplitude
54
Table 1. Nonlinear results in surveys investigated
55
CUGINI'S MINIMAL CHANGE HYPERTENSIVE RETINOPATHY, RESOLVED
CHRONOBIOLOGICALLY WHILE DIPPING FAILS, SUPPORTS THE CONCEPT OF
'PRE-HYPERTENSION'
Germaine Cornélissen1
, Pietro Cugini2
, Jarmila Siegelova3
, Bohumil Fiser3
, Franz Halberg1
1
University of Minnesota, Minneapolis, Minnesota, USA
2
University "La Sapienza", Rome, Italy
3
Masaryk University, Brno, Czech Republic
"Prehypertension" is a term with many meanings considered from at least two perspectives,
one homeostatic (1-8), the other chronobiologic (9-18). The homeostatic view bases the diagnosis
of the condition on the repeated measurement of the blood pressure (BP), starting with no more
than one or a few measurements at a few office visits and managing the patient on this basis. (The
Austrian guidelines deserve credit for requiring a minimum of 30 measurements, without,
however, specifying their timing and thus not prescribing sampling that would allow an
assessment of periodic variations [7]). Prehypertension, homeostatically, can be, e.g., a systolic (S)
blood pressure (BP) between 120 and 139 mmHg and/or diastolic (D) BP between 80 and 89
mmHg (3). Only in special cases does the homeostatic physician offer the opportunity of a 24-hour
profile as the (false) gold standard and still usually interprets the results by 24-hour, if not
spotcheck-derived, 24-hour means, daytime and nighttime means, according to several national
and international guidelines, also recommending fixed, time-invariant target BPs for human adults
of any gender, age (above 18 years) and ethnicity. By contrast, in his 1880 thesis for his medical
degree, Ignaz Zadek explicitly did not wish to evaluate "the" BP of a given patient, but rather the
variability (13, 14), and Theodore C. Janeway in 1904 argued for the collection of enough data to
evaluate periodic variations before seeing a patient (15).
56
Pietro Cugini, former Professor of Internal Medicine at the University of Rome 'La
Sapienza', went an important step further by formulating what, according to his co-authors (GC
and FH), may be called "Cugini's minimal-change hypertensive retinopathy", based on elevations
of both the circadian rhythm-adjusted BP mean (MESOR), M, and amplitude, A, as compared to
control subjects without retinopathy. Cugini used chronobiologic methodology but applied it to
only 24-hour records and interpreted the results in the light of conventional guidelines. From a
methodological viewpoint, his studies are valuable since he shows an inferentially-validated
statistically significant difference in M and a difference in circadian A in patients with Cugini's
minimal-change hypertensive retinopathy. Several inferences can be drawn from his study:
1. By the time of a minimal retinopathy, there can be not only an elevated BP-M, but also an
increased circadian A as compared to controls, and it will be important to see in longitudinal
studies whether the rise in circadian A precedes that in MESOR as suggested by other evidence
(16-18).
2. As Cugini himself notes, the number of subjects (and, we add, the duration of each record) are
to be extended with a hybrid (linked cross-sectional) design for additional, more reliable 7-daybased
cases as well as for reference values, and further for starting longitudinal surveillance of BP
not only in adults but also in primary and secondary education; under-diagnosis of hypertension
has been reported for children and adolescents (19).
3. The elevation in circadian amplitude of BP is relatively modest and on the average remains
below available thresholds derived from clinically healthy gender-, age- and ethnicity-matched
peers (20, 21). The elevation in circadian A does not involve an increased risk of hard events until
a threshold is reached (20), i.e., until there is an overswinging (CHAT, short for circadian hyperamplitude-tension).
Cugini's pre-hypertension is hence an optimal stage when the individual
should be treated to reverse the path toward a high risk of ischemic stroke, myocardial infarction,
kidney disease and blindness, since CHAT can be treated (9, 22; cf. 23).
4. Methodologically, Figure 1 shows that from the viewpoint of a classification based on the
nocturnal fall in BP in terms of averages (original data were not available to GC and FH), the
57
subjects with retinopathy are dippers while those without retinal involvement are non-dippers. In
this analysis, a classification based on the day-night ratio (dipping) actually misleads while earlier
it only failed to work in predicting hard events, when a chronobiologic approach worked (24-26).
Figure 1: Subjects with minimal change retinopathy have daytime mean values of systolic blood pressure (SBP)
higher than those without retinopathy (top left); a dipping classification not only fails to resolve prehypertension,
being normal in the presence of a minimal-change retinopathy, yet abnormal in the absence of minimal change
retinopathy (bottom). Chronobiology shows an increase in circadian amplitude as well as MESOR, in the
presence (PNS) versus the absence (TNS) of minimal retinopathy, top right. © Halberg.
58
Conclusion. Cugini's prehypertension should stimulate ophthalmologists to recommend 7day/24-hour
chronobiologically interpreted ABPM, in order to detect and treat variability disorders
of children and adolescents, as well as adults, and vice versa to recommend an ophthalmological
examination whenever a BP variability disorder is found.
Supported by MSM0021622402
REFERENCES
1. O'Brien E, Staessen J. Normotension and hypertension defined by 24-hour ambulatory blood
pressure monitoring. Blood Pressure 1995; 4: 266-282.
2. Japanese Society of Hypertension Guidelines Subcommittee for the Management of
Hypertension. Guidelines for the management of hypertension for general practitioners.
Hypertension Res 2001; 24: 613-634.
3. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW,
Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, National Heart, Lung, and Blood Institute
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure. National High Blood Pressure Education Program Coordinating Committee.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289 (19): 2560-2672.
4. Guidelines Committee, 2003 European Society of Hypertension. European Society of
Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21:
1011-1053.
5. O'Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, Mengden T, Myers M,
Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P,
European Society of Hypertension Working Group on Blood Pressure Monitoring. European
Society of Hypertension recommendations for conventional, ambulatory and home blood
pressure measurement. J Hypertension 2003; 21(5): 821-848.
59
6. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps
SG, Roccella EJ. Recommendations for blood pressure measurement in humans and
experimental animals. Part I: Blood pressure measurement in humans: a statement for
professionals from the Subcommittee of Professional and Public Education of the American
Heart Association Council on High Blood Pressure Research. Circulation 2005; 111: 697-
716.
7. Magometschnigg D. Definition und Klassifikation der Hyperton 2004; 8 (1): 12-13.
8. Deutsche Hochdruckliga e.V. (DHL) und Deutsche Hypertoniegesellschaft (DHL/DHG).
Leitlinien zur Hypertonie. www.paritaet.org/RR-Liga Guidelines.htm 2006.
9. Halberg F, Cornélissen G, International Womb-to-Tomb Chronome Initiative Group:
Resolution from a meeting of the International Society for Research on Civilization Diseases
and the Environment (New SIRMCE Confederation), Brussels, Belgium, March 17-18, 1995:
Fairy tale or reality ? Medtronic Chronobiology Seminar #8, April 1995, 12 pp. text, 18
figures. http://www.msi.umn.edu/~halberg/
10. Cugini P, Petrangeli CM, Capodaglio FP, Chiera A, Cruciani F, Turri M, Gherardi F, Santino
G. 'Retinopatia tensiva a lesioni minime' e pre-ipertensione arteriosa: evidenze dal
monitoraggio della pressione arteriosa in soggetti reputati normotesi a 'rischio zero'. Rec
Progr Med 1997; 88: 11-16.
11. Cugini P, Fontana S, Pellegrino AM, Lucia P, Stirati G, Cruciani F, Scibilia G, Pachi A. Il
concetto di "pre-ipertensione arteriosa" alla luce del monitoraggio ambulatorio non-invasivo
della pressione arteriosa. Rec Prog Med 1998; 89: 559-568.
12. Cugini P, Cruciani F, Turri M, Regine F, Gherardi F, Petrangeli CM, Gabrieli CB. 'Minimalchange
hypertensive retinopathy' and 'arterial pre-hypertension', illustrated via ambulatory
blood-pressure monitoring in putatively normotensive subjects. International Ophthalmology
1999; 22(3): 145-149.
13. Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch'chen Apparates.
Berlin, med. F., Diss., 25. Nov 1880. Berlin: Schumacher; 1880. 48 p.
60
14. Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch'chen Apparates. Z
klin Med 1881; 2: 509-551.
15. Janeway TC. The clinical study of blood pressure. New York: D. Appleton & Co.; 1904. 300
pp.
16. Halberg J, Halberg E, Hayes DK, Smith RD, Halberg F, Delea CS, Danielson RS, Bartter
FC. Schedule shifts, life quality and quantity modeled by murine blood pressure elevation
and arthropod lifespan. Int J Chronobiol 1980; 7: 17-64.
17. Kumagai Y, Shiga T, Sunaga K, Cornélissen G, Ebihara A, Halberg F. Usefulness of
circadian amplitude of blood pressure in predicting hypertensive cardiac involvement.
Chronobiologia 1992; 19: 43-58.
18. Watanabe Y, Cornélissen G, Halberg F, Bingham C, Siegelova J, Otsuka K, Kikuchi T.
Incidence pattern and treatment of a clinical entity, overswinging or circadian
hyperamplitudetension (CHAT). Scripta medica (Brno) 1997; 70: 245-261.
19. Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and
adolescents. JAMA 2007; 298: 874-879.
20. Cornélissen G, Halberg F, Schwartzkopff O, Delmore P, Katinas G, Hunter D, Tarquini B,
Tarquini R, Perfetto F, Watanabe Y, Otsuka K. Chronomes, time structures, for
chronobioengineering for "a full life". Biomed Instrum Technol 1999; 33: 152-187.
21. Hillman DC, Cornélissen G, Scarpelli PT, Otsuka K, Tamura K, Delmore P, Bakken E,
Shinoda M, Halberg F, International Womb-to-Tomb Chronome Initiative Group. Chronome
maps of blood pressure and heart rate. University of Minnesota/Medtronic Chronobiology
Seminar Series, #2, December 1991, 3 pp. of text, 38 figures.
22. Shinagawa M, Kubo Y, Otsuka K, Ohkawa S, Cornélissen G, Halberg F. Impact of circadian
amplitude and chronotherapy: relevance to prevention and treatment of stroke. Biomedicine
& Pharmacotherapy 2001; 55 (Suppl 1): 125s-132s.
23. Halberg F, Cornélissen G, Halberg J, Schwartzkopff O. Pre-hypertensive and other
variabilities also await treatment. Am J Medicine 2007; 120: e19-e20.
doi:10.1016/j.amjmed.2006.02.045.
61
24. Otsuka K, Cornélissen G, Halberg F. Predictive value of blood pressure dipping and
swinging with regard to vascular disease risk. Clinical Drug Investigation 1996; 11: 20-31.
25. Bingham C, Cornélissen G, Chen C-H, Halberg F. Chronobiology works when day-night
ratios fail in assessing cardiovascular disease risk from blood pressure profiles. Abstract, III
International Conference, Civilization diseases in the spirit of V.I. Vernadsky, People's
Friendship University of Russia, Moscow, Oct. 10-12, 2005, p. 111-113.
26. Cornélissen G, Halberg F, Otsuka K, Singh RB, Chen CH. Chronobiology predicts actual
and proxy outcomes when dipping fails. Hypertension 2007; 49: 237-239.
doi:10.1161/01.HYP.0000250392.51418.64.
62
CONFIDENCE INTERVALS ASSESS THE CONGRUENCE OF PERIODS
CHARACTERIZING MANY NEONATAL TRANSDISCIPLINARY NIKITYUK CYCLES
Inna Malkova1
, Elena V. Syutkina1
, Germaine Cornélissen2
, Anatoly Masalov3
, Bohumil Fiser4
,
Jarmila Siegelova4
, Franz Halberg2
1
Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia
2
Halberg Chronobiology Center, University of Minnesota, Minneapolis, Minnesota, USA
3
Lebedev Physical Institute, Moscow, Russia, 4
Masaryk University, Brno, Czech Republic
Background
A prolonged global solar activity cycle with a period of 16 to 18 years, reportedly associated
with holes in the topology of the sun's corona and manifested in the distribution of open magnetic
field structures (1), as reviewed by Nayar (2), complements the about (~) 10.5- and ~21-year
Schwabe and Hale cycles of Wolf's relative sunspot numbers and their signatures in human growth
and development described by Nikityuk.
Materials and Methods
We use Marquardt's approach for extended cosinor-implemented linear-nonlinear
rhythmometry on data on body length at birth recorded from random samples from 25-150
babies/year in Moscow, Russia during 1874 to 1985 and shorter series from Alma Ata, Kazakstan
(3-7).
Metaanalytical Problem
In body length in Moscow, a period (τ) of 20.28 years (y) with a 95% confidence interval (in
parentheses) extending from 18.76 to 21.88 y is found for boys and a period of 20.78 (19.05,
22.78) y for girls. The corresponding values for Russians in Alma Ata are τ = 17.77 (14.00, 20.07)
y for boys and 17.75 (15.21, 21.08) y for girls. For Kazaks in Alma Ata, the τ for boys = 21.24
(18.39, 24.09) y and for girls 21.45 (15.44, 27.45) y. Without confidence intervals, uncertainties
are missed: one would postulate that a signature of a global solar cycle characterizes Russian boys
and girls in Alma Ata and a Hale cycle in Moscow, suggesting indeed a plausible geographic
63
difference. The difference between Russians and Kazaks in Alma Ata, in point estimates of τ may
suggest an ethnic difference. In addition to putative ethnic and geographic differences there is also
a likely effect to be anticipated from the different lengths of the time series analyzed. The
confidence intervals may be questioned since the time series are non-stationary and one remedy
may be to compute the periods on sections of the time series and to summarize them by
population-mean cosinor. In the latter case, they will be most likely different and probably yet
wider. An about 15-year cycle in premature labor in data of the senior author (IM) has the same
uncertainty.
New results
By examining additional data covering 22 more years with gaps, IM prolonged an already
unique Nikityuk series and confirms the main inferences drawn cautiously from the original data
covering more than a century. The ubiquity in neonatal events of signatures of Schwabe and Hale
cycles is thus extended to many variables of pediatric interest: incidences of toxicosis, miscarriage,
anemia, respiratory infection, pyelonephritis, gestosis, premature labor, premature membrane
rupture, Apgar-1, Apgar-5 scores, birth weight, height, head and chest circumference. Her work is
dedicated to the memory of Boris Nikityuk (10.X.1933-30.IX.1998), the late professor and head of
the Department of Anatomy and Anthropology of the Russian Academy of Physical Education,
Moscow and the President-Founder of the International Academy of Integrative Anthropology.
Supported by MSM0021622402
REFERENCES
1. Markov VI, Sivaraman KR. New results concerning the global solar cycle. Solar Phys 1989;
123: 367-380.
2. Prabhakaran Nayar SR. Periodicities in solar activity and their signature in the terrestrial
environment. ILWS Workshop, Goa, February 19-24, 2006. 9 pp.
3. Halberg F, Cornélissen G, Otsuka K, Syutkina EV, Masalov A, Breus T, Viduetsky A, Grafe
A, Schwartzkopff O. Chronoastrobiology: neonatal numerical counterparts to Schwabe's 10.5
64
and Hale’s 21-year sunspot cycles. In memoriam Boris A. Nikityuk. Int J Prenat Perinat
Psychol Med 2001; 13: 257-280.
4. Cornélissen G, Halberg F. Chronomedicine. In: Armitage P, Colton T, editors. Encyclopedia
of Biostatistics, 2nd ed. Chichester, UK: John Wiley & Sons Ltd; 2005. p. 796-812.
5. Refinetti R, Cornélissen G, Halberg F. Procedures for numerical analysis of circadian
rhythms. Biological Rhythm Research 2007; 38 (4): 275-325.
http://dx.doi.org/10.1080/09291010600903692
6. Halberg F, Cornélissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T,
Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB,
Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O,
Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group.
Chronobiology's progress: season's appreciations 2004-2005. Time-, frequency-, phase-,
variable-, individual-, age- and site-specific chronomics. J Applied Biomedicine 2006; 4: 1-
38. http://www.zsf.jcu.cz/vyzkum/jab/4_1/halberg.pdf
7. Halberg F, Cornélissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T,
Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB,
Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O,
Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group.
Chronobiology's progress: Part II, chronomics for an immediately applicable biomedicine. J
Applied Biomedicine 2006; 4: 73-86. http://www.zsf.jcu.cz/vyzkum/jab/4_2/halberg2.pdf
65
RENAL FAILURE AND LONG-TERM EXERCISE TRAINING – A REVIEW
Masahiro Kohzuki
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate
School of Medicine, Sendai, Japan
INTRODUCTION
The exercise capacity of the patients with renal dysfunction declines and this
phenomenon is distinctly related to the extent of renal function deterioration. It is suggested
that appropriate exercise training may improve the physical strength and the quality of life in
patients with chronic renal failure（CRF）besides the improvement of glucose and lipid
metabolism.
PRESENT STATUS
However, it is required to consider the influence of exercise on renal function
thoroughly, because acute exercise causes proteinuria and decreases renal blood flow and
glomerular filtration rate. At present, there are few reports concerning the optimal intensity
and duration of exercise training for patients with CRF. Moreover, there has been no definite
conclusion as to whether or not chronic exercise training（EX）has any renal protective
effect in animal models of CRF. Recently, the renal and peripheral effects of long-term
moderate to intense exercise training in various rat models of CRF has been extensively
reported. The effects of a combination of EX and rennin-angiotensin system
inhibitors（ARI）on renal function were also assessed. The results indicated that moderate to
intense EX and ARI can yield a renal protective effect in some models. They also suggested
that the simultaneous treatment of moderate EX and ARI provided a greater renoprotective
effect than treatment by ARI alone.
66
CONCLUSION
Further investigations will be needed to examine the mechanism of the renal
protective effect of EX. A better understanding of the mechanism may lead to improved
exercise strategies and the establishment of a renal rehabilitation regime for CRF patients.
Supported by MSM0021622402
REFERENCES
1. Cheema B, Abas H, Smith B, O'Sullivan A, Chan M, Patwardhan A, Kelly J, Gillin A,
Pang G, Lloyd B, Singh MF. Progressive exercise for anabolism in kidney disease
(PEAK): a randomized, controlled trial of resistance training during hemodialysis. J
Am Soc Nephrol. 2007; 18(5): 1594-601.
2. Davison SN. Facilitating advance care planning for patients with end-stage renal
disease: the patient perspective. Clin J Am Soc Nephrol. 2006; 1(5): 1023-8.
3. Dodson JL, Diener-West M, Gerson AC, Kaskel FJ, Furth SL. An assessment of
health related quality of life using the child health and illness profile-adolescent
edition in adolescents with chronic kidney disease due to underlying urological
disorders. J Urol. 2007; 178(2): 660-5; discussion 665.
4. Gaudino M, Girola F, Piscitelli M, Martinelli L, Anselmi A, Della Vella C, Schiavello
R, Possati G. Long-term survival and quality of life of patients with prolonged
postoperative intensive care unit stay: unmasking an apparent success. J Thorac
Cardiovasc Surg. 2007; 134(2): 465-9.
5. Giordano M, Tirelli P, Ciarambino T, Gambardella A, Ferrara N, Signoriello G,
Paolisso G, Varricchio M. Screening of depressive symptoms in young-old
hemodialysis patients: relationship between Beck Depression Inventory and 15-item
Geriatric Depression Scale. Nephron Clin Pract. 2007; 106(4): 187-92.
67
6. Molsted S, Prescott L, Heaf J, Eidemak I. Assessment and clinical aspects of healthrelated
quality of life in dialysis patients and patients with chronic kidney disease.
Nephron Clin Pract. 2007; 106(1): 24-33.
7. Neumann ME Finding 'hope' for understanding kidney disease. Nephrol News Issues.
2007; 21(5): 64-66.
68
1
NON-INVASIVE IMAGING TECHNIQUES IN CASES OF CARDIAC FAILURE
Wolf Jean-Eric.a
, Dobsak Petr.b
, Barthez Olivier.a
, Eicher Jean-Christophe a
,
Siegelova Jarmila.b
a
IInd
Department of Cardiology, University Hospital of Dijon, France
b
Department of Functional Diagnostics and Rehabilitation, St.Anna Faculty Hospital
in Brno, Czech Republic
Introduction
Echocardiography is a traditional noninvasive "imaging" method that provides useful
information for the management of heart failure. Its potential applications range from
diagnosis to therapeutic decisions to the monitoring of therapy. Although great strides have
been made in the understanding and treatment of heart failure, its incidence is increasing and,
along with this increase, a growing number of patients are presenting with additional co-
morbidities.
Recent advances in the imaging techniques helped much the diagnosis of cardiac
failure (1). These modern imaging modalities combine classic echocardiography (TTE, TEE)
computed tomography (CT) and MRI, are constantly used to confirm the existence, to precise
the etiologies, mechanisms and prognosis of the cardiac failure. Although echocardiography is
still the first line modality used, imaging is often sub-optimal especially in non-echogenic
patients. Computed tomography and MRI are second line imaging modalities that have the
ability to overcome the limitations of echocardiography.
The mentioned non-invasive imaging techniques allow the doctors to follow with
precision their patients on treatment and to reach some therapeutic indications (implantable
cardioverter-defibrillators, for instance) depending on the data obtained from the imaging
technique (2).
In this short review we will present and precise their use in clinical practice
summarized in the Table 1.
69
2
Methods compared
Table 1
Echocardiography Nuclear
cardiology
CT MRI
Ventricular function
-systolic
-global and regional
-dyssynchrony
-diastolic
Aetiology
-ischaemic heart disease
-valvular heart disease
-cardiomyocardiopathy
Prognosis
Follow-up
+++
+++
++
+++
++
+++
+
++
+++
+++
++
+
+
++
-
-
++
++
+ ?
+ ?
-
-
++
+
?
?
-
+++
+++
?
?
++
+
++
++
++
+ to +++ : increasing interest for the technique for each item
Discussion
The most frequently used technique for assessment of the left ventricle status in heart
failure is still echocardiography (TTE or TEE). These techniques are widely available, but
image acquisition depends on the operator and the acoustic window. Reproducibility is
reasonable in normal ventricles, but the quantification of volumes and mass relies on
geometric assumptions that do not apply to ventricles undergoing asymmetric cardiac
remodeling such as in cardiomyopathy (3). Cardiovascular magnetic resonance is independent
of geometric assumptions (4) and has been shown to be accurate and reproducible (5). The
published reproducibility data for echocardiography and newly acquired MRI data in patients
with heart failure suggested recently the improved reproducibility for MRI, leading to
significant reductions in sample sizes for drug trials (6). However, there are no reports of
direct comparison of reproducibility of MRI with echocardiography in the same group of
patients. Thus, it should be of interest to perform a head-to-head comparison between these
techniques and to determine the influence of heart size, shape, and mass on the results in
70
3
normal subjects and patients with dilated or hypertrophied hearts. The methods of nuclear
cardiology such as thallium SPECT have been proposed to predict the reversibility of left
ventricular dysfunction after revascularization. These techniques permit differentiation of
viable from nonviable myocardium; however few studies have directly compared their
accuracy in the same patients (7, 8). It is now widely accepted that the techniques used in
nuclear cardiology have comparable accuracy for prediction of reversibility of global left
ventricular dysfunction after revascularization (9, 10).
The combination of cardiac MRI and multi-slice CT can complement the diagnostic
information obtained by echocardiography and invasive cardiac catheterization. Postoperative
imaging of CHD is especially enhanced by the spin echo MRI techniques, while
gradient cine-echo MRI imaging allows functional information that is not encumbered by
geometric assumptions (11). Phase contrast (velocity encoding) cardiac MRI data can provide
information about flow, allowing accurate determination of regurgitation and shunt volume.
Gadolinium enhanced MRI or three-dimensional reconstructed images from multi-slice CT
angiography allow excellent delineation of vascular structures in complex heart disease.
Coronary imaging, while possible with both modalities, appears more facile with fast CT
imaging (11).
Conclusion
The presented data obtained by various techniques in patients with heart failure should
be interpreted in the context of locally available techniques. It is necessary to point out that
there are very wide variances in several parameters such as volumes and ejection fraction
between techniques used, which are most marked in comparisons using echocardiography.
This suggests that cardiovascular magnetic resonance could be recommended as a preferred
technique for volume and ejection fraction estimation in heart failure patients, because of its
3D approach for non-symmetric ventricles and superior image quality.
Supported by MSM0021622402
71
4
References
1. Higgins CB. Which standard has the gold? J Am Coll Cardiol 19 (1992), pp. 1608–
1609.
2. Habib G, Tribouilloy C, Lafitte S. The best of echocardiography in 2006. Arch Mal
Coeur Vaiss. 2007 Jan;100 Spec No 1:9-17.
3. Gordon EP, Schnittger I, Fitzgerald PJ, Williams P, Popp RL. Reproducibility of left
ventricular volumes by two-dimensional echocardiography. J Am Coll Cardiol 2
(1983), pp. 506–513.
4. Allison JD, Flickinger FW, Wright CJ, Falls DG, Prisant LM, VonDohlen TW, Frank
MJ. Measurement of left ventricular mass in hypertrophic cardiomyopathy using MRI:
comparison with echocardiography. Magn Reson Imaging 11 (1993), pp. 329–334
5. Longmore DB, Klipstein RH, Underwood SR, Firmin DN, Hounsfield GN, Watanabe
M, Bland C, Fox K, Poole-Wilson PA, Rees RS. Dimensional accuracy of magnetic
resonance in studies of the heart. Lancet 1 (1985), pp. 1360–1362.
6. Bellenger NG, Grothues F, Smith G, Pennell DJ. Quantification of right and left
ventricular function by MRI. Herz 25 (2000), pp. 392–399
7. Rehr RB, Mallow CR, Filipchuk NG, Peshock RM. Left ventricular volumes
measured by MR imaging. Radiology 156 (1985); 285-8.
8. Mogelvang J, Stockholm KH, Saunamaki K, Reimer A, Stubgaard M, Thomsen C,
Fritz-Hansen P, Henriksen O. Assessment of left ventricular volumes by magnetic
resonance in comparison with radionuclide angiography, contrast angiography and
echocardiography. Eur Heart J 13 (1992), pp. 1677–1683.
9. Tamborini G, Galli CA, Maltagliati A, Andreini D, Pontone G, Quaglia C, Ballerini G,
Pepi M. Comparison of feasibility and accuracy of transthoracic echocardiography
versus computed tomography in patients with known ascending aortic aneurysm. Am J
Cardiol. 2006 Oct 1;98(7):966-9. Epub 2006 Aug 22.
10. Semelka RC, Tomei E, Wagner S, Mayo J, Caputo G, O’Sullivan M, Parmley WW,
Chatterjee K, Wolfe C, Higgins CB , Interstudy reproducibility of dimensional and
functional measurements between cine magnetic resonance imaging studies in the
morphologically abnormal left ventricle. Am Heart J 119 (1990), pp. 1367–1373.
11. Samyn MM. A review of the complementary information available with cardiac
magnetic resonance imaging and multi-slice computed tomography (CT) during the
study of congenital heart disease. Int J Cardiovasc Imaging. 2004 Dec;20(6):569-78.
72
EFFECT OF LOW VOLTAGE ELECTRICAL STIMULATION ON ANGIOGENESIS
IN RAT SKELETAL MUSCLE
Makoto NAGASAKA, Masahiro KOHZUKI
The Department of Internal Medicine and Rehabilitation Science, Graduate School of
Medicine, Tohoku University of Sendai, Japan
INTRODUCTION
LVES (Low voltage electrical stimulation) in skeletal muscle at a level far below the threshold
of muscle contraction has been reported to promote local angiogenesis. However the
mechanism underlying the promotion of local angiogenesis by LVES has not been fully
elucidated.
AIM
We evaluated whether angiogenic factors, such as VEGF (vascular endotherial growth factor),
HGF (hepatocyte growth factor) and FGF (fibroblast growth factor), and other
disadvantageous factor, such as inflammation { IL6 (Interleukin-6)}, and hypoxia {HIF-
1α(hypoxia-inducible factor 1α)} contribute to the local angiogenesis by LVES. Moreover
there are some reports that both HVES (high voltage electrical stimulation) up-regulates
VEGF and we compared the effects of LVES to that of HVES on the induction of the
angiogenic factors.
ANIMALS AND METHODS
We completely excised bilateral femoral arteries of the Male Sprague-Dawley Rats. After the
operation, the electrodes were implanted onto the center of the fascia of the bilateral TA
(tibialis anterior) muscles, tunneled subcutaneously and exteriorized at the level of the
scapulae. The rats were randomly divided into 3 groups. In the first group, the TA muscles
73
were continuously stimulated at a 50-Hz stimulus frequency, with a 0.1 V stimulus strength
and no interval (C-LVES). In the second group, rats were stimulated with 50Hz, 0.1V stimuli
at two-hour intervals (I-LVES). In the third group rats were stimulated with a 10Hz, 3V
stimulus at two-hour intervals (I-HVES).
RESULTS
The VEGF levels were significantly increased in C-LVES, I-LVES and I-HVES stimulated
muscles compared with that of the controls. However there was not significantly different in
the VEGF level among 3 conditions. The HGF level was significantly increased only in CLVES
stimulated muscles compared with that of the controls whereas were not increased in ILVES
and in I-HVES. C:F ratio (Capillary to muscle fiber ratio) of stimulated muscles were
increased about 2 fold compared with the unstimulated muscles in C-LVES and I-HVES,
whereas was not increased in I-LVES. On the contrary, there was no difference in FGF, IL6,
and HIF-1α between the LVES group and control group.
CONCLUSION
In conclusion, both LVES and HVES are useful to induce VEGF and angiogenesis. Moreover
LVES might be better for ischemic disease than HVES, as HVES causes discomfort and
muscle atrophy.
Supported by MSM0021622402
74
REFERENCES
1. Dobsak P, Nagasaka M, Siegelova J, Kohzuki M, Imachi K, Jancik J. PROMOTION
OF ANGIOGENESIS AND BLOOD SUPPLY RESTORATION IN ISCHEMIC
SKELETAL MUSCLE OF RAT AFTER LOW-VOLTAGE ELECTRICAL
STIMULATION. Atherosclerosis Supplements 2005; 6(1):16-17.
2. Nagasaka M, Kohzuki M, Dobsak P, Fujii T, Mori, Ichie M. THE EFFECT ON
ANGIOGENESIS BY CONTINUOUS ELECTRICAL STIMULATION OF
SKELETAL MUSCLE OF RAT: THE CHANGE OF BLOOD FLOW BY
ELECTRICAL STIMULATION (Japanese). Japanese Journal of Rehabilitation
Medicine 2005; 41(suppl.): S291.
3. Nagasaka M, Kohzuki M, Ito O, Minami N, Dobsak P. THE EFFECT ON
ANGIOGENESIS BY CONTINUOUS ELECTRICAL STIMULATION OF
SKELETAL MUSCLE OF RAT: THE BLOOD FLOW OF HEALTHY MEN BY
ELECTRICAL STIMULATION (Japanese). Japanese Journal of Rehabilitation 2005;
41(suppl.): S292.
4. Nagasaka M, Kohzuki M, Dobsak P, Imachi H, Minami N. NEW STRATEGY OF
PHYSICAL THERAPY: EFFECT OF LOW-VOLTAGE ELECTRICAL
STIMULATION ON ANGIOGENESIS IN RAT SKELETAL MUSCLE. In:
Proceedings of the 3rd
World Congress of the International Society of Physical and
Rehabilitation Medicine Sao Paulo 2005. Monduzzi Editore: 845-48. ISBN 88-7587-
137-X
5. Nagasaka M, Kohzuki M, Fujii T, Kanno S, Kawamura T, Onodera H, Itoyama Y,
Ichie M, Sato Y. EFFECT OF LOW-VOLTAGE ELECTRICAL STIMULATION ON
ANGIOGENIC GROWTH FACTORS IN ISCHAEMIC RAT SKELETAL MUSCLE.
Clin Exp Pharmacol Physiol. 2006; 33(7): 623-7.
6. Nagasaka M, Kohzuki M, Minami N, Kanazawa M, Dobsak P, Siegelova J. LOWVOLTAGE
ELECTRICAL STIMULATION AS A NEW TREATMENT FOR
ISCHEMIC DISEASE ON HYPERTENSIVE ATHEROSCLEROSIS. Journal of
Hypertension 2006; 24(suppl.6): S237.
75
1
CIRCADIAN BLOOD PRESSURE VARIATION ANALYZED FROM 7-DAY
MONITORING
Jarmila Siegelová, Jiří Dušek, Bohumil Fišer, Pavel Homolka, Pavel Vank, Michal Mašek,
Alena Havelková, Germaine Cornelissen*, Franz Halberg*
Department of Functional Diagnostics and Rehabilitation, Masaryk University Brno, St. Anna
Faculty Hospital Brno, Czech Republic, *University of Minnesota, USA
INTRODUCTION
Franz Halberg, Germaine Cornelissen and BIOCOS scientific group provided strong evidence
for the need to account for day-to-day changes in blood pressure and heart rate variables in
the similar way as a circadian assessment considers the hour-to-hour variability [1-5]. The
evidence led to the recommendation of around-the-clock monitoring for 7 days at the outset
[6,7], to be continued whenever needed, until monitoring for a lifetime becomes more readily
feasible.
By 1988, major findings had been summarized in a volume of annotated illustrations
[8]. Methodology had developed concomitantly under Halberg chronobiology center
leadership in Minnesota University. In particular, the "sphygmochron" [9] was introduced.
The sphygmochron is a computer summary of results from chronobiological analyses
performed on BP and HR data collected around the clock by ambulatory monitoring. Two
approaches are possible, one parametric (model-dependent), the other non-parametric (modelindependent).
The parametric approach entails the least-squares fit of a two-component model
consisting of cosine curves with periods of 24 and 12 hours. Estimates are obtained for the
MESOR (midline-estimating statistic of rhythm), a rhythm-adjusted mean, and for the
amplitude and (acro)phase of each component, measures of (half) the extent of predictable
change within a cycle, and of the timing of overall high values recurring in each cycle,
respectively.
The relationship between age and circadian blood pressure (BP) variation was the aim of the
present study.
76
2
METHODS
One hundred and eighty-seven subjects (130 males, 57 females), twenty years to seventy
seven years old, were recruited for seven-day BP monitoring. Colin medical instruments
(Komaki, Japan) were used for ambulatory BP monitoring (oscillation method, 30-minute
interval between measurements). Sinusoidal curve was fitted (minimum square method) and
mean value and amplitude of the curve (double amplitude corresponds to the night-day
difference) were evaluated every day of monitoring. Average 7-day values of the mean (M)
and of double amplitude (2A) for systolic BP (SBP), diastolic BP (DBP) and heart rate (HR)
were determined for each subject.
RESULTS
Mean values of MESOR (±SD) for the whole group of healthy people were: SBP- 127±8
mmHg, DBP – 79±6 mmHg, HR – 70±6 bpm. Mean values of double circadian amplitude
were: SBP – 21±7 mmHg, DBP – 15±5 mmHg, HR – 15±6 bpm. The linear relationship
between MESOR of SBP and age (r=0.341, p< 0.001) and DBP and age (r=0.384, p<0.001)
was found (difference between the age of twenty years and seventy seven years: SBP - 16,
DBP-12 mmHg). Double circadian amplitude of SBP and DBP was increasing with age up to
35 years, then the curve remained relatively flat up to 55 years (maximum at 45 years) and
then decreased again (difference between 45 and 77 years: SBP- 13 mmHg, DBP-12 mmHg).
Heart rate MESOR and double circadian ampitude were age-independent.
Mean values of SBP and DBP were increasing with age up to 75 years, but night-day
difference of SBP and DBP reached the maximum value at 45 years and then decreased.
77
3
Figure 1. The circadian rhythm analysis according to non-parametric approach.
MESOR - rhythm-adjusted 24-hour mean.
Amplitude –half of total predictable change in rhythm, definied by rhythmic function fitted to
data and expressed in original or relative units, e.g., as percentage of series mean or MESOR.
Acrophase- Timing of peak value of the rhythm. Halberg cosinor analysis.)
78
4
Relationship between mean SBP and age
y = 0,0097x
2
- 0,5478x + 129,57
R
2
= 0,2151
0,000
20,000
40,000
60,000
80,000
100,000
120,000
140,000
160,000
0 10 20 30 40 50 60 70 80
year
mmHg
Figure 2 . Relationship between MESOR of systolic blood pressure(SBP, mmHg), measured
by 7 day ambulantory blood pressure monitoring, and age (years) of the subjects.
79
5
Relationship between mean DBP and age
y = -0,0074x
2
+ 0,9514x + 52,901
R
2
= 0,3844
0
20
40
60
80
100
120
0 10 20 30 40 50 60 70 80
year
mmHg
Figure 3. Relationship between MESOR of diastolic blood pressure (DBP, mmHg), measured
by 7 day ambulantory blood pressure monitoring, and age (years) of the subjects.
80
6
Relationship between MESOR HR and age
y = 0,0264x + 69,931
R2
= 0,0026
50
60
70
80
90
100
110
15 25 35 45 55 65 75 85
AGE
bpm
Figure 4. Relationship between MESOR of heart rate (HR, bpm), measured by 7-day
ambulatory blood pressure monitoring, and age (years) of the subjects
81 7
Figure 5. Relationship between circadian amplitude of systolic blood pressure (SBP,
mmHg), measured by 7-day ambulantory blood pressure monitoring, and age (years) of the
subjects.
Circadian amplitude SBP and age
y = -0,0059x
2
+ 0,5526x - 0,6632
R
2
= 0,108
0,0
5,0
10,0
15,0
20,0
25,0
15 25 35 45 55 65 75
year
mmHg
82
8
Figure 6. Relationship between circadian amplitude of diastolic blood pressure (DBP,
mmHg), measured by 7-day ambulatory blood pressure monitoring, and age (years) of the
subjects.
Circadian amplitude DBP and age
y = -0,0068x
2
+ 0,5899x - 3,3926
R
2
= 0,1671
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
15 25 35 45 55 65 75
year
mmHg
83
9
Circadian amplitude HR and age
y = -0,0392x + 9,6173
R
2
= 0,0281
0
2
4
6
8
10
12
14
16
18
20
15 25 35 45 55 65 75 85
AGE
CD-A
Figure 7. Relationship between circadian amplitude of heart rate (bpm, HR), measured by 7day
ambulatory blood pressure monitoring, and age (years) of the subjects.
84
10
DISCUSSION
There is a growing body of evidence suggesting that time structures in us and around
us are intrically interwoven. Most if not all components of variation found in biota are also
found in the environment, and vice versa [10]. For instance, about daily changes are seen in
almost every biological variable under 24-hour synchronized conditions. It has also long been
known that the phase of circadian rhythms can be manipulated by changing the phase of the
environmental cycles [11]. At least for the case of circadian rhythms, their genetic inheritance
has been demonstrated on a molecular basis [12,13], suggesting that the influence from the
environment has been acquired genetically during the course of evolution.
The mapping of chronomes should benefit our understanding of human health and disease in
several ways. The study of human chronomes can serve the derivation of refined reference
values to better define health and to identify pre-disease, so that prophylactic interventions
can be instituted as early as possible, preferably before disease sets in [14-16]. The focus is
thus put on pre-habilitation, in the hope that the need for re-habilitation will thereby be
reduced [17,18,19].
Several studies [20, 21] comparing the classification of patients based on single office
measurements with that based on ambulatory monitoring for one to seven days suggest that
the incidence of misdiagnosis is around 40%, in keeping with the 48% response to placebo in
the Australian Therapeutic Trial [22,23]. Comparison of circadian characteristics from day to
day in records spanning at least two days further indicates the shortcomings of monitoring
limited to a single 24-hour span [24,25,26]. Prolonging the monitoring from one to two days
reduces the uncertainty in the estimation of circadian parameters by about 35% [27], whereas
further information on the biological week [28,29,30,31] requires monitoring for at least 7
days, the current recommendation of BIOCOS for everybody at the outset [32]. It is now
widely accepted that prognosis of target organ damage is by far superior when it is based on
around the clock monitoring than on single office measurements [33,34,35].
The mistaken impression that the circadian variation in blood pressure and heart rate is
sufficiently stable to be approximated by a single 24-hour profile stems in large part from the
use of statistical methods on groups of subjects rather than focusing on the individual patient.
Correlation analyses applied to large groups of subjects with a wide range of average values
emphasize similarity. Statistical analyses focusing on individual differences observed from
85
11
one profile to another, however, yield information more likely to help the patient in need of
treatment [24]. Several case reports document this point [16, 36, 37,38, 39]. Continued
monitoring is the most logical solution.
An important distinction needs to be made between lessons learned from large clinical
trials and their application for the individual patient. Differences and trends uncovered in
studies on groups, even when each subject provides only one or a few measurements, cannot
be similarly assessed in medical practice when a decision needs to be made for treating the
individual patient. In order to be able to reach an informed decision for the given patient,
serial rather than single data should be collected. When time series are available, it becomes
possible to assess risk elevation or the response to treatment for that particular patient.
Our study made possible not only to confirm the increase of systolic and diastolic blood
pressure with age but also to describe the age dependence of the circadian amplitude. Mean
values of SBP and DBP were increasing with age up to 75 years, but night-day difference of
SBP and DBP reached the maximum value at 45 years and then decreased.
Supported by MSM0021622402
REFERENCES
1. Halberg F. Some physiological and clinical aspects of 24-hour periodicity. J-Lancet
(Minneapolis) 73: 20-32, 1953.
2. Halberg F. Chronobiology. Ann Rev Physiol 31: 675-725, 1969.
3. Cornélissen G, Halberg E, Halberg Francine, et al. Chronobiology: a frontier in biology
and medicine. Chronobiologia 16: 383-408, 1989.
4. Halberg F, Cornélissen G. Chronobiology, rhythms, clocks, chaos, aging, and other
trends. In: Maddox G. (ed.) Encyclopedia of Aging, 3rd ed. Springer, New York, 2001,
pp. 196-201.
5. Halberg F, Cornélissen G, Otsuka K, et al., International BIOCOS Study Group. Crossspectrally
coherent ~10.5- and 21-year biological and physical cycles, magnetic storms
and myocardial infarctions. Invited presentation, NATO Advanced Study Institute on
Space Storms and Space Weather Hazards, Crete, Greece, June 19-29, 2000.
Neuroendocrinol Lett 21: 233-258, 2000.
86 12
6. Halberg F, Cornélissen G, Wall D et al. Engineering and governmental challenge: 7day/24-hour
chronobiological blood pressure and heart rate screening. Biomedical
Instrumentation & Technology 36: Part I, 89-122, Part II, 183-197, 2002.
7. Cornélissen G, Delmore P, Halberg F. Health Watch 3. University of
Minnesota/Medtronic, Minneapolis, MN, 31 pp., 2004.
8. Halberg F, Cornélissen G, Halberg E, Halberg J, Delmore P, Shinoda M, Bakken E.
Chronobiology of human blood pressure. Medtronic Continuing Medical Education
Seminars, 1988, 4th ed., 242 pp.
9. Halberg F, Bakken E, Cornélissen G, et al. Chronobiologic blood pressure assessment
with a cardiovascular summary, the sphygmochron. In: Blood Pressure Measurements
(Meyer-Sabellek W, Anlauf M, Gotzen R, Steinfeld L, eds), Steinkopff Verlag,
Darmstadt, FRG, 1990, pp. 297-326.
10. Halberg F, Cornélissen G, Otsuka K, Watanabe Y, Delyukov A, Gorgo Y, Zhao ZY,
Weydahl A, Sothern RB, Siegelova J, Fiser B, Dusek J, Syutkina EV, Perfetto F,
Tarquini R, Singh RB, Rhees B, Lofstrom D., Lofstrom P, Sonkowsky R, Johnson
PWC, Schwartzkopff O, International BIOCOS Study Group. Cross-spectrally coherent
~10.5- and 21-year biological and physical cycles, magnetic storms and myocardial
infarctions. Neuroendocrinoogy Letters 2000; 21: 233-258.
11. Halberg F. Chronobiology. Annual Reviews of Physiology 1969; 31: 675-725.
12. Pennisi E. Multiple clocks keep time in fruit fly tissues. Science 1997; 278: 1560-1561.
13. Plautz JD, Kaneko M, Hall JC, Kay SA. Independent photoreceptive circadian clocks
throughout Drosophila. Science 1997; 278: 1632-1635.
14. Halberg F, Cornélissen G, Carandente A, Bakken E, Young E. Chronobiologic
perspectives of international health care reform for the future of children.
Chronobiologia 1993; 20: 269-275.
15. Cornélissen G, Delmore P, Bingham C, Rutledge G, Kumagai Y, Kuwajima I, Suzuki
Y, Kuramoto K, Otsuka K, Scarpelli PT, Tarquini B, Cagnoni M, Garcia L, Zaslavskaya
RM, Syutkina E, Carandente F, Rapoport SI, Romanov YA, Tamura K, Bakken E,
Halberg F. A response to the health care crisis: a ‘health start’ from ‘womb to tomb’.
Chronobiologia 1993; 20: 277-291.
16. Cornélissen G, Otsuka K, Halberg F. Blood pressure and heart rate chronome mapping:
a complement to the human genome initiative. In: Chronocardiology and
Chronomedicine: Humans in Time and Cosmos, Otsuka K, Cornélissen G, Halberg F
(eds.), Life Sciences Publishing, Tokyo, 1993, pp. 16-48.
87 13
17. Cornélissen G, Halberg F, Schwartzkopff O, Delmore P, Katinas G, Hunter D, Tarquini
B, Tarquini R, Perfetto F, Watanabe Y, Otsuka K. Chronomes, time structures, for
chronobioengineering for "a full life". Biomedical Instrumentation & Technology 1999;
33: 152-187.
18. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y,
Halhuber M, Müller-Bohn T, Delmore P, Siegelova J, Homolka P, Fiser B, Dusek J,
Sanchez de la Peña S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F,
Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and
governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate
screening: Part I. Biomedical Instrumentation & Technology 2002; 36: 89-122.
19. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y,
Halhuber M, Müller-Bohn T, Delmore P, Siegelova J, Homolka P, Fiser B, Dusek J,
Sanchez de la Peña S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F,
Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and
governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate
screening: Part II. Biomedical Instrumentation & Technology 2002; 36: 183-197.
20. Kumagai Y, Kuwajima I, Suzuki Y, Kuramoto K, Otsuka K, Cornélissen G, Halberg F.
Untenable acceptance of casual systolic/diastolic blood pressure readings below 140/90
mm Hg. Chronobiologia 1993; 20: 255-260
21. Schaffer E, Cornélissen G, Rhodus N, Halhuber M, Watanabe Y, Halberg F. Outcomes
of chronobiologically normotensive dental patients: a 7-year follow-up. J American
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22. Management Committee. Australian National Blood Pressure Study: The Australian
Therapeutic Trial in Mild Hypertension. The lancet (June 14) 1980: 1261-1267.
23. Halberg F, Cornélissen G, Halberg E, Halberg J, Delmore P, Shinoda M, Bakken E.
Chronobiology of human blood pressure - Medtronic Continuing Medical Education
Seminars, 1988, 4th ed., 242 pp.
24. Cornélissen G. Instrumentation and data analysis methods needed for blood pressure
monitoring in chronobiology. In: Scheving LE, Halberg F, Ehret CF (eds).
Chronobiotechnology and Chronobiological Engineering. Dordrecht, The Netherlands:
Martinus Nijhoff, 1987, pp. 241-261.
25. Tamura K, Wu J, Cornélissen G, Halberg F. Agreement between consecutive
ambulatory 24-hour blood pressure and heart rate profiles in Japanese hospital staff.
Progress in Clinical and Biological Research 1990; 341A: 263-272.
88
14
26. Watanabe Y, Cornélissen G, Halberg F, Bingham C, Siegelova J, Otsuka K, Kikuchi T.
Incidence pattern and treatment of a clinical entity, overswinging or circadian
hyperamplitudetension (CHAT). Scripta medica 1997; 70: 245-261.
27. Halberg F, Scheving LE, Lucas E, Cornélissen G, Sothern RB, Halberg E, Halberg J,
Halberg Francine, Carte J Jr, Straub KD, Redmond DP. Chronobiology of human blood
pressure in the light of static (room-restricted) automatic monitoring. Chronobiologia
1984; 11: 217-247.
28. Carandente F, Cornélissen G, Halberg F Further data and analyses. Chronobiologia
1994; 21: 311-314.
29. Halberg F, Cornelissen G, Raab F, Schaffer E, Siegelova J, Fiser B, Dusek J, Prikryl P,
Otsuka K. Automatic physiologic 7-day monitoring and chronobiology. Japanese J of
Electrocardiology 1995; 15 (Suppl. 1): S-1-5 - S-1-11.
30. Siegelova J, Homolka P, Dusek J, Fiser B, Cornélissen G, Halberg F. Extracircadian-tocircadian
variance transpositions early and vice versa late in life in the human
circulation. Proceedings, 1st International Symposium, Workshop on
Chronoastrobiology & Chronotherapy (Satellite Symposium, 7th Annual Meeting,
Japanese Society for Chronobiology), Kudan, Chiyodaku, Tokyo, 11 Nov 2000, pp. 58-
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31. Singh RB, Cornélissen G, Siegelova J, Homolka P, Halberg F. About half-weekly
(circasemiseptan) pattern of blood pressure and heart rate in men and women of India.
Scripta medica 2002; 75: 125-128.
32. Halberg F, Smith HN, Cornélissen G, Delmore P, Schwartzkopff O, International
BIOCOS Group. Hurdles to asepsis, universal literacy, and chronobiology—all to be
overcome. Neuroendocrinology Letters 2000; 21: 145-160.
33. Mancia G, Gamba PL, Omboni S, Paleari F, Parati G, Sega R, Zanchetti A. Ambulatory
blood pressure monitoring. J Hypertension (Suppl) 1996; 14: S61-S66.
34. Mallion JM, Baguet JP, Siche JP, Tremel F, De Gaudemaris R. Clinical value of
ambulatory blood pressure monitoring. J Hypertension 1999; 17: 585-595
35. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage.
Hypertension 2000; 36: 894-900.
36. Halberg F, Cornélissen G, International Womb-to-Tomb Chronome Initiative Group.
Resolution from a meeting of the International Society for Research on Civilization
Diseases and the Environment (New SIRMCE Confederation), Brussels, Belgium,
89
15
March 17-18, 1995: Fairy tale or reality? Medtronic Chronobiology Seminar #8, April
1995, 12 pp. text, 18 figures.
37. Cornélissen G, Halberg F. Impeachment of casual blood pressure measurements and the
fixed limits for their interpretation and chronobiologic recommendations. Annals. New
York Academy of Sciences 1996; 783: 24-46.
38. Cornélissen G, Halberg F, Hawkins D, Otsuka K, Henke W. Individual assessment of
antihypertensive response by self-starting cumulative sums. J Medical Engineering &
Technology 1997; 21: 111-120
39. Halberg F, Cornélissen G, Otsuka K, Katinas GS, Schwartzkopff O, Halpin C,
Mikulecky M, Revilla M, Siegelova J, Homolka P, Dusek J, Fiser B, Singh RB.
Chronomics detects altered vascular variabilities constituting risks greater than
hypertension: with an illustrative case report. In: Mitro P, Pella D, Rybar R, Valocik G
(eds). Proceedings, 2nd
Congress on Cardiovascular Diseases, Kosice, Slovakia, 25-27
April 2002. Bologna: Monduzzi Editore, 2002, pp. 223-258.
90
ANALYSIS OF BAROREFLEX FUNCTION BY MEANS OF MATHEMATICAL
MODEL
Bohumil Fišer, Jarmila Siegelová, Jiří Dušek, Michal Pohanka, Michal Mašek, Josef Barák,
Jiří Moudr, Germaine Cornelissen, Franz Halberg
Dept Physiology, Dept. Functional Investigations and Rehabilitation, Faculty of Medicine,
Masaryk University, Brno
INTRODUCTION
It is generally believed that the primary function of baroreflex is a short time stabilization of
blood pressure. Reevaluation of all functions of baroreflex by means of simple mathematical
model of circulation was the aim of the present study.
METHODS
The simple mathematical model of circulation consists of three equations:
CO = (AP – VP) / TPR, M = Ca * AP + Cv * VP, CO = k * VP, where CO = cardiac output, AP
= arterial pressure, VP = venous pressure, TPR = total peripheral resistance, M = total volume of
blood in arterial and venous beds, Ca = arterial bed capacity (0.006 l/mmHg), Cv = venous bed
capacity (0.6 l/mmHg), k = constant proportional to myocardial contractility (1). The following
states are modeled: 1. Rest (AP = 100 mmHg, CO = 5l/min, M = 3.6 l = total blood volume –
volume of blood in heart and lungs). 2. Immediately after baroreceptors denervation (increase in
blood pressure 50 mmHg caused by increased TPR). 3. Several days after baroreceptors
denervation (return of blood pressure to the original level caused by natriuresis and by
corresponding decrease in blood volume). 4. Physical exercise before baroreceptors denervation
(increase of cardiac output to 20 l/min at constant blood pressure, k and TPR are calculated, other
91
values equal to rest values). 5. Physical exercise several days after baroreceptors denervation
(TPR and k equal to values at exercise before denervation).
RESULTS
The results are seen in Table 1.
Rest Exercise
Before
denervation
Immediately
after
Several
days after Exercise before
Exercise
after
AP mmHg 100 150 100 100 72.6
CO l/min 5 4.5 3 20 13.1
M l 3.6 3.6 2.4 3.6 2.4
TPR
mmHg*min/l 19 32.3 32.3 4.75 5.3
K
l/(min*mmHg) 1 1 1 4 4
VP mmHg 5 4.5 3 5 3.3
Despite the same value of cardiac contractility indicator k and the same decrease of TPR caused
by vasodilatation in working muscles as before denervation the cardiac output is one third lower
after baroreceptors denervation. This demonstrates the disadvantage of baroreceptor denervation
and so the main function of the baroreflex.
DISCUSSION
The elimination of baroreflex by cutting of baroreceptors efferents in animal experiments elicits
immediately an increase in blood pressure of approximately 50 mmHg. Blood pressure returns to
the original level by means of natriuresis during few days. The trade off is a decrease of blood
volume, which causes the decrease of cardiac output during exercise. This indicates that the
primary function of baroreflex is the vasodilatation by suppression of activity of vasomotor level
nerves. Therefore blood volume is held on a sufficiently high level.
92
The baroreceptors cannot measure the absolute values of blood pressure. The baroreceptors
resetting during the night serves to the recalibration (2). The set point is approximately 50 mmHg
under the value of blood pressure at which the suppression of vasomotor activity is completely
abolished. The combined action of baroreflex control and endocrine humoral blood pressure by
kidneys secure relatively low blood pressure at blood volume sufficiently high for increased
cardiac output during exercise. Relatively low blood pressure decreases the oxygen consumption
of heart muscle and protects the brain vessels. The latter function is more important. Blood
pressure in giraffe is much higher than in man and other mammals without negative
consequences. The importance of brain blood vessels protection demonstrates the localization of
baroreceptors in vessels conducting blood to the brain. The brain perfusion is fine tuned by
autoregulation during several seconds. We have demonstrated this reaction in man several years
ago (3). This autoregulatory reaction disappears in hypertensives (4). It is seen not only from our
study, but also the observation of inadequate perfusion of brain in hypertensives after abrupt
decrease of blood pressure by antihypertensive treatment demonstrates this fact. The low
baroreflex gain insufficiently protects the human body from increase in blood pressure caused by
psychological stress or by obesity. We have demonstrated in children and young adults that low
baroreflex gain and obesity are two independent risk factors for high blood pressure (5). This
study also solved “the egg and hen problem”. Low baroreflex gain was observed also in white
coat hypertension, it means before the increased blood pressure remodeled the carotic sinus wall
(6).
CONCLUSION
In conclusion, the model simulation revealed the common regulation of blood pressure and blood
volume by baroreflex and kidneys as a primary function of baroreflex. The second important
function is protection of brain vessels against the loss of autoregulatory ability, which is
important for adequate supply of the brain with oxygen and nutrition. Baroreflex maintains
adequate protection against hypertension in primitive civilizations but at obesity and/or
psychological stress the low baroreflex gain is an independent risk factor for hypertension.
Supported by MSM0021622402
93
REFERENCES
1. Fišer B. Teoretické problémy terapie hypertenze řešené pomocí jednoduchého
matematického modelu. Čas. Lék. Čes. 115,1976,(33-34), p.1008-1011.
2. Siegelová, J., Fišer, B., Dušek, J., et al. 24-hodinové monitorování krevního tlaku u
pacientů s esenciální hypertenzí. Vnitř Lék, 1993, 39, p. 183-190.
3. Savin E., Siegelova J., Fišer B., Bonnin P.: Intra- and extracranial artery blood flow
velocity during sudden blood pressure decrease in humans. Eur. J. Appl. Physiol. 76,
1997, 289-293.
4. Siegelová J., Fišer B., Dušek J., Al-Kubati M.: Die Baroreflexsensitivitätsmessung bei
Patienten mit essentieller Hypertonie: Einfluss von Enalapril. Nieren und
Hochdruckkrankheiten 24(1), 1995: p. 20-22.
5. Honzíková N., Nováková Z., Závodná E. Paděrová J., Lokaj P., Fišer B., Balcárková P.,
Hrstková H. Baroreflex sensitivity in children, adolescents, young adults with essential
and white–coat hypertension. Klinische Paediatrie, 218, 2006, (4), p. 237-242.
6. Cornélissen G., Delcourt A., Toussaint G.et al. Opportunity of detecting pre-hypertension:
world wide data on blood pressure overswinging. Biomedicine and pharmacotherapy,59,
2005; Suppl. 1: p. 152 – 157.
94
FUNCTIONAL IMPAIRMENT AND QUALITY OF LIFE IN PATIENTS AFTER
ACUTE STROKE
Martina Tarasová, Jana Nečasová, Robert Mikulík,
Michal Pohanka, Mohsin Kaid Ali Hashim, Lenka Drliková, Barbora Bártlová, Eva
Nosavcovová, Nabil Abdulah Ibrahim Al-Mahmodi, Abdul Karim Al Fadhli, Farag Hassan
Anbais, Ashref Ali Erajhi, Petr Pospíšil, Lumír Konečný, Jarmila Siegelová
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk
University, St. Anna Teaching Hospital, Brno, CZ
INTRODUCTION
Stroke is a leading cause of disability among elderly people. In addition to physical,
emotional and social consequences, the economic impact of stroke is tremendous. The
incidence of stroke increases markedly with age ageing populations expose an increasing
number of people to the risk of stroke in western countries (13).
Little is known about the effectiveness of long-term stroke physiotherapy. There are no
generally accepted guidelines that determine the optimal timing, intensity or duration of
rehabilitation. We have not found any data what kind of physiootherapy is most beneficial and
resource-efficient for the patients with residual disabilities living in their homes. Several
reports have addressed the need for psychological support and enhancing social activities in
order to reach the ultimate goal in stroke rehabilitation. Many stroke patients fail to resume
full lives, and a major negative impact of stroke on family functioning is not an infrequent
phenomenon. Therefore, stroke rehabilitation requires a long-term perspective, extending to
several years after the onset of stroke (13).
The role of rehabilitative efforts has been widely recognized as being essential in the acute
stage of stroke. The beneficial effects of stroke unit rehabilitation have been well documented
by several workers. Treatment of acute stroke patients in stroke units has been shown to
reduce mortality, length of hospital stay, discharge rate to nursing homes and cost. Functional
recovery has been significantly greater and more rapid in a stroke unit in comparison with
general wards. Treatment in stroke units has increased the proportion of patients able to live at
home long after their stroke (14).
95
When we speak about quality of life, we usually pursue the impact of the disease of a person
on his or her physical or mental health, way of life and sense of contentment with life (8).
The definition of quality of life is based on the Maslow's theory of hierarchy of needs, i.e.
fulfilment of basic physiological needs (need of satiation, sleep, easing the pain) is the
condition of stimulation and fulfilment of more subtle needs (need of security, need of
relationship with other people, need of self-esteem) (8). Quality of life is regarded as a
multidimensional quantity and usually it is defined as „subjective evaluation of own living
situation“. It includes therefore not only the sense of physical health and absence of symptoms
of the disease or treatment, but, in global approach, also mental health, social functioning,
religious and economic aspects, etc. (9). Other factors influencing quality of life include age,
sex, polymorbidity, family situation, preferred values, economic situation, education,
religiosity, cultural background, etc. Overall quality of life is then a complex of the abovementioned
factors (10, 11).
The question which factors influence quality of life and have an impact on activities of
daily life in different situations and circumstances is studied systematically in many countries
of the world and widely published. With questionnaires enabling quality of life conditioned by
health state to be marked, we have available a tool allowing us to quantify and assess the
condition of our patients (Health Related Quality of Life – HRQOL) before our therapeutic
and nursing interventions as well as after them (2). By means of the short-form HRQOL
questionnaires - SF-36 we can evaluate the results of medical and social interventions (3). The
short form of the questionnaire (Short Form 36 Health Subject Questionnaire, SF 36) is the
most frequently applied generic questionnaire. This questionnaire is a tool being used often
for evaluation of quality of life in various branches of medicine due to its good informative
value. The assessment is carried out in 8 domains or categories, namely physical activity,
physical role, pain, general health evaluation, vitality, social activity, emotional role, mental
health (7, 2).
AIM
The first aim of this study was as to evaluate the questionnaire of quality of life (participation)
- Index of overall quality of life (SF-36 short-form) in patients after acute stroke (CMP) with
moderately serious and light affection according to FIM (Functional independence measure)
who were hospitalized in the Ist
neurological clinic of St. Anna Teaching Hospital in Brno.
96
The second aim was to answer the question whether quality of life depends on functional
impairment of patients with stroke tested by means of Functional Impairment measure (FIM),
which was measured in the period when they were released from the clinic.
METHODS
Characteristic of the patients with stroke
The set consisted of 40 patients of average age 60,1 ± 11,8 years (range 30 - 88 years),
with the diagnosis I 60 – I 69, generally affected central nervous system (CNS) with
impairment of motor functions, with moderately serious functional affection according to
FIM, who were hospitalized with acute stroke in the Ist
Neurological clinic of St. Anna
Teaching Hospital in Brno. The set consisted of 20 women of average age 59.6 ± 12.4 years
and of 20 men of average age 61.5 ± 11.3 years.
The questionnaire FIM was originally given to 96 patients who were instructed to send it
back to the clinic within 1 - 2 months after their hospitalization in the Ist
neurological clinic
for the subsequent statistical data processing, only 40 questionnaires were answered, i.e.
approx. 42 %.
In the course of hospitalization in the clinic the whole set was subjected to evaluation of
impairment by means of the test Functional independence measure (FIM) – measurement of
functional independence.
The average time of hospitalization was 13.2 ± 6.5 days (with a minimum of 3 days and
maximum of 34 days) and 34 patients were allowed home, 6 were transferred to facilities for
subsequent care.
Methods of evaluation
At the beginning of rehabilitation care and at the finishing of hospitalization disability of
patients was tested by means of Functional independence measure (FIM).
Patients were intensively treated with drugs and physiotherapeutic procedures based on
specialized methods of physiotherapy based on neurophysiological approach. There are
following methods used:
Conventional - range of motion/strengthening exercises, training in mobility for functional
independence
97
Neurodevelopmental Training (NDT) - also known as the Bobath technique. This technique
was developed in the 1940s and the principle is to reduce muscle spasticity by focusing on
normal patterns of movement.
Proprioceptive neuromuscular facilitation (Knott & Voss) - relies on quick stretching and
manual resistance of muscle activation of the limbs in functional directions, which often are
spiral and diagonal in direction.
Brunnstrom technique - facilitates synergistic patterns of movement that develop during
recovery from hemiplegia (paralysis of one side of the body). Development of flexor and
extensor synergies is encouraged during early recovery with the hope that synergic
activation of muscles will transition into voluntary activation of movements
Rood technique - modifies movement with cutaneous sensory stimulation
When these approaches to stroke recovery are compared to each other, no one method
appears to be more effective than another. However, NDT alone may require prolonged
periods of time to produce functional results which may be accomplished faster in conjunction
with other methods. Some rehabilitation facilities also incorporate biofeedback into their
program to complement other types of therapy (15).
The patients being released from the clinic were given the questionnaire Index of overall
quality of life (SF-36) as a device assessing participation with the instruction to send it back
to the clinic within 1 - 2 months after their hospitalization in the Ist
Neurological clinic for the
subsequent statistical data processing. The evaluation was carried out in 8 above-mentioned
categories.
Numerical expression of dimensions of quality of life – individual dimensions influencing
quality of life are based on the questionnaire SF-36 and are calculated as average values of
specific questions from the questionnaire being structured in the particular way. These
dimensions have the values from 0 to 100. A lower value means generally a worse value of
the given dimension and decreases overall quality of life, a higher value means generally a
better value of the given dimension and increases overall quality of life.
The study was approved by the local ethical commission, the examined patients signed
informed approval.
Statistical processing
Statistical processing was made by using the program Microsoft Excel, version 2002 and
the program Statistica, version 7. The results are presented as the average and the standard
98
deviation (x±SD). The values of individual dimensions were determined by means of the
program SF-36® Health Survey Scoring Demonstration (12). Then we determined correlation
coefficient and statistical significance in selected relations.
RESULTS
The functional condition evaluation by means of FIM at the beginning of rehabilitation care
(admission) and at the releasing from the clinic (discharge) is presented in the whole set (40
patients), in the sets of women (20 patients) and men (20 patients), in the patients under 70
years of age (25 patients) and in the patients of 70 and more years of age (15 patients).
Graph 1. Evaluation FIM at the beginning of care (admission) and at the releasing from the
clinic (discharge); *p < 0.05
18
28
38
48
58
68
78
88
98
108
118
whole set women men under 70 years 70 years and
more
hodnotaFIM
enter
discharge
The file of 40 delivered questionnaires of quality of life SF 36 was subdivided, because of
comparison, into subgroups according to age (age over 70 and under 70 years) and according
to sex (sets of women and men).
Evaluation of individual items in the questionnaire quality of live SF 36:
Table 1 Values of individual categories in quality of live SF 36 and general physical and
* * * *
*
99
mental health in the whole set.
PF RP BP GH VT SF RE MH PCS MCS
average 45.8 29.4 54.8 46.9 46.4 53.8 45.8 58.8 35.4 42.6
SD
± 30.9 ± 36.6 ± 28.6 ± 19.9 ± 21.2 ± 30.5 ± 41.8 ± 18.1 ± 10.9 ± 9.7
Explanation: x - average, SD - standard deviation, PF - Physical Functioning, RP - Role-Physical, BP - Bodily
Pain, GH - General Health, VT - Vitality, SF - Social-Functioning, RE - Role-Emotional, MH - Mental Health,.
PCS - Physical Component Summary, MCS - Mental Component Summary
Table 2 Values of individual categories in quality of live SF 36 and general physical and
mental health in the set of women.
PF RP BP GH VT SF RE MH PCS MCS
average 43.8 35 50.1 47.2 46.8 51.9 56.7 58.6 34.3 43.9
SD
± 32.4 ± 40.1 ± 26 ± 20.3 ± 19.4 ± 33.3 ± 43.4 ± 19.8 ± 11.3 ± 9.2
Explanation: x - average, SD - standard deviation, PF - Physical Functioning, RP - Role-Physical, BP - Bodily
Pain, GH - General Health, VT - Vitality, SF - Social-Functioning, RE - Role-Emotional, MH - Mental Health,.
PCS - Physical Component Summary, MCS - Mental Component Summary
Table 3 Values of individual categories in quality of live SF 36 and general physical and
mental health in the set of men
PF RP BP GH VT SF RE MH PCS MCS
average 47.8 23.8 59.4 46.6 46 55.6 34.9
59
34.3 43.9
SD
± 30.2 ± 32.9 ± 31 ± 20 ± 23.4 ± 28.2 ± 38.2 ± 16.8 ± 11.3 ± 9.2
Explanation: x - average, SD - standard deviation, PF - Physical Functioning, RP - Role-Physical, BP - Bodily
Pain, GH - General Health, VT - Vitality, SF - Social-Functioning, RE - Role-Emotional, MH - Mental Health,.
PCS - Physical Component Summary, MCS - Mental Component Summary
Table 4 Values of individual categories in quality of live SF 36 and general physical and
mental health in the set of patients under 70 years of age
100
101
36 in the studied sets
whole set
x
women
x
men
x
age to 70 years
x
age 70 and more
years
x
PF 45.8 43.8 47.8 47.6 42.7
RP 29.4 35 23.8 32 25
BP 54.8 50.1 59.4 54.7 54.8
GH 46.9 47.2 46.6 46.3 47.8
VT 46.4 46.8 46 45.2 48.3
SF 53.8 51.9 55.6 50.5 59.2
RE 45.8 56.7 34.9 45.3 46.7
MH 58.8 58.6 59 56.3 62.9
PCS 35.4 34.3 34.3 36.4 33.9
MCS 42.6 43.9 43.9 41.1 45.2
Explanation: x - average, SD - standard deviation, PF - Physical Functioning, RP - Role-Physical, BP - Bodily
Pain, GH - General Health, VT - Vitality, SF - Social-Functioning, RE - Role-Emotional, MH - Mental Health,.
PCS - Physical Component Summary, MCS - Mental Component Summary
Elderly patients (70 and more years of age) evaluated their Physical Component Summary as
the worst one. The greatest differences are apparent in perception of “Role-Emotional” in the
sets of men and women; the difference is 21.8 in favour of women with better subjective
perception. Then quite a big difference (11.2) was recorded in the category “Role-Physical”,
that is evaluated better by women, and “Bodily Pain”, being better tolerated by men with the
difference 9.3. Similar results, without major differences between individual sets, were found
in the items “Vitality” and “General Health”.
We answered also the question whether quality of life in our set being tested depends on the
final functional condition of patients with stroke tested by means of FIM when they were
released from the clinic and whether general physical health correlates with mental health.
The results of correlation analysis are presented in Table 7.
Table 7 Dependence of final functional condition according to FIM on index of general
mental and physical health SF 36
102
FIM x PCS FIM x MCS PCS x MCS
correlation coefficient
r
correlation coefficient
r
correlation coefficient
r
whole set 0.175 NS 0.053 NS 0.485**
set of women 0.123 NS 0.096 NS 0.557*
set of men 0.237 NS -0.015 NS 0.469*
set under 70 0.197 NS 0.067 NS 0.685**
Set of 70 and more 0.074 NS -0.355 NS 0.112 NS
Explanation: FIM - Functional independence measure, PCS - Physical Component Summary, MCS - Mental
Component Summary, r - correlation coefficient, NS - not statistically significant, * statistically significant p <
0,05, ** statistically significant p < 0,01
There is no correlation between FIM and SF 36. Correlation between PCS and MCS shows
that physical health in younger patients influences significantly mental health. In patients over
70 years of age we have not found a significant correlation, influence of physical health on
mental health is not important.
DISCUSSION
Evaluation of quality of life becomes an integral part of studies monitoring on a long-term
basis health state of patients in various branches of medicine, with the conception of quality
of life including a wide range of life perception (7).
Even if evaluation of the degree of impairment is of an essential significance for
assessment of seriousness of the stroke, it cannot implicate all main factors influencing
quality of life. Not only health state, but also social and economic conditions, mental health,
fulfilment of aims in life, culture and value system in various geographical conditions are
ranked among them. Quality of life is a subjectively perceived standard of life by which
people assess their physical, emotional and social abilities (4).
Our results show that patients after stroke reach a lower number of points in subjective
evaluation of quality of life in all aspects, as it was expected in generic disorders bringing on
disability (6).
As to the age and quality of life, elderly patients arrived at worse evaluation almost in all
items; it can be caused by development of the disease, higher number of associated
103
complications in higher age, impaired ability of adaptation, lower motivation, etc.
As to the differences between sexes, we found them mostly in the parameter „RoleEmotional“;
women evaluated this item by 21.8 points better than men, and in “RolePhysical”
where evaluation of women was better by 11.2 in comparison with men. Also
perception of pain was worse in women (a difference against men was 9.3).
In the other parameters there were not significant differences in the monitored sets.
As to the evaluation of dependence of functional condition of patients with CMP tested by
means of FIM when they were released from the clinic and quality of life evaluated according
to SF 36, a statistically significant relation was not possible to be demonstrated.
As the questionnaire SF-36 is a simple and cheap device for determination of quality of
life, the information provided by this questionnaire could be used both before the specific
therapy and after it for determination of changes in quality of life by way of changes in points
of patients, concurrently with clinical measurements of seriousness of the disease (1).
The main reason of evaluation of quality of life in patients is assessment of the treatment
effect. In available foreign literature we can notice the effort to assess the treatment effect in a
more complex way, not only according to somatic and laboratory markers, but also by means
of evaluation of quality of life. In our conditions evaluation of quality of life is carried out
mainly on account of the research and is not a usual part of the treatment. Our study shows
that there is no connection between functional condition of patients and subjectively
perceived quality of life. That is why a complex evaluation of quality of life requires
combination of both questionnaire methods (FIM and SF 36).
CONCLUSION
According to our results there is no correlation between the Functional independence
measure (FIM) and Index of overall quality of life (SF-36 short-form). Correlation between
Physical Component (PCS) and Mental Component Summary (MCS) shows that in younger
patients physical health influences significantly mental health. In patients over 70 years of age
we have not found a significant correlation, the effect of physical health on mental health is
not significant.
Supported by MSM0021622402
104
LITERATURE
1) Kvalita života u pacientů s Charcot-Marie-Tooth chorobou, in. 2005, 65, p.922-924.
http://websiska.cz/ct/dokumenty/vysledky_studie_u_italskych_pacientu_s_CMT.pdf
2) Petr, P.: Dotazník SF-36 o kvalitě života podmíněné zdravím (The SF-36
Questionnaire of the Health related Quality of Life). Kontakt, 2000, 2(1): p. 26-29.
Petr, P., a kol..:Regionální standard Kvality života podmíněné zdravím (The Regional
Standard of Health Related Quality of Life). Kontakt 2001, 3 (3): p. 146-150.
3) Last, J. M.: A dictionary of epidemiology III, Ed. Oxford Univ. Press, 1995, 180 p.
4) Kolektiv autorů: Životní styl a obezita - longitudiální epidemiologická studie
prevalence obezity. ČLS JEP, Česká obezitologická společnost. Praha, 2006, 63 p.
5) Kalová, H. et al.: Kvalita života u chronických onemocnění ve světle novějších
modelů zdraví
6) Slováček, J. et al.: Kvalita života nemocných - jeden z důležitých parametrů
komplexního hodnocení léčby. Vojenské zdravotnické listy, ročník LXXIII, 2004, 1, p.
6-9.
7) Zittoun, R. et al.: Assessment of quality of life during intensive chemotherapy bone
marrow transplantation. Psychooncology, 1999, vol. 8, no. 1, p. 64−73.
8) Quality of Life for Patients with Chronic Illness.
http://www.nih.gov/ninr/about/legislation/chronic_illnesss.htm
9) Stáblová, A.: Kvalita života dialyzovaných nemocných. UK FTVS Praha, Laboratoř
sportovní motoriky. www.ftvs.cuni.cz
10) Curtis, J.R., et al.: Measure of the Quality of Dying and Death: Initial Validation Using
After-Death Interviews with Family Members. J. Pain Sympt. Management, 2002, 24,
1, p. 17−31.
11) SF-36® Health Survey Scoring Demonstration
http://www.sf-36.org/ SF-36® Health Survey Scoring Demonstration.htm
12) Pitkänen,K.: Stroke rehabilitation in the elderly. A controlled study of the effectiveness
and costs of a multidimensional intervention. Series of Reports, No 52, Department of
Neurology, University of Kuopio. 2000.
13) Indredavik B, Bakke F, Slordahl SA, Rokseth R, Håheim LL: Stroke unit treatment:
10-year follow-up. Stroke 1999; 30: 1524-1527.
15) Rehabilitation of Motor Deficit after stroke –Untertanding stroke rehabilitation. In:
105
http://www.medifocushealth.com/NR020/Approaches-to-Stroke- Rehabilitation
Rehabilitation-of-Motor-Deficits-after-Stroke.php
Summary
The aim of this study was to evaluate the questionnaire of quality of life (SF-36 short-form) in
patients after acute stroke and to compare the results with Functional Impairment Measure
(FIM).
Methods: We examined 40 patients with acute stroke by means of questionnaire FIM and the
questionnaire of quality of life (SF-36 short-form).
Results and conclusion: We have not found after rehabilitation any correlation between FIM
and index of quality of live in patients after acute stroke. The correlation between physical
component and mental component according to FIM summary was found in younger patients
under 70 years of age.
Key words: stroke, quality of life, physiotherapy, functional impairment measurement
106
1
WATER IMMERSION AND PHYSIOTHERAPY IN PATIENTS WITH PARKINSON
DISEASE
Petr Pospíšil,1,2
Lumír Konečný,1,2
, Marie Zmeškalová2
, Hana Srovnalová3
, Ivana Rektorová3
,
Eva Nosavcovová2
, Michaela Sosíková2
, Petr Dobšák1,2
, Jarmila Siegelová1,2
,
Dept. of Functional Diagnostics and Rehabilitation1
, Department of Physiotherapy2
, Dept. of
Neurology3
, Medical Faculty, Masaryk University, St. Anna Faculty Hospital in Brno,
Czech Republic
INTRODUCTION
Rigidity, postural instability, bradykinesis and tremor are well known basic symptoms of
Parkinson’s disease (PD). Higher incidence of cardiovascular diseases belongs to other
characteristics that are, together with respiratory complications, the most common cause of
death in PD (1, 2).
Positive effect of exercise therapy was reported repeatedly (3, 4, 5, 6). Aerobic exercise
therapy in a swimming pool with warm water is also recommended. However, there is no
evidence on cardiovascular parameters reaction to water immersion in PD patients in
scientific literature sources. We have already shown the reaction of cardiovascular parameters
in patients with cardiovascular disease in our previous study (7).
AIM
Elucidation of reaction of cardiovascular parameters to water immersion of lower parts of the
body and thorax in patients with PD was the aim of the present study.
107
2
METHODS
9 patients with the diagnosis of PD were examined at the Dept. of Neurology, St. Anna
Faculty Hospital in Brno, Czech Republic. Stable medication without changes during the last
month, Hoehn and Yahr Score < 3 and suitability for exercise therapy in the swimming pool
were assessed as entrance criteria of this study.
Basic statistic parameters of the tested group of PD patients are presented as mean values ±
standard deviations (SD): age 71±7 years, duration of disease 7±3 years, Hoehn and Yahr
score 2.2±0.7.
Exercise therapy in the swimming pool was realized with the frequency of once a week for
the period of 12 weeks. Each exercise therapy unit lasted 40 minutes. It consisted of 10
minutes of outdoor warm-up phase and 30 minutes of aerobic exercise in the swimming pool
aimed at balance improvement, rigidity and hypokinesis management, muscular imbalances
and other gross and fine motor skills improvement. This phase was followed by 15 minutes of
relaxation in supine position in a dry wrap.
Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were measured.
Mercury manometer was used for the measurement of blood pressure, Polar tester for the
measurement of heart rate, rate x product (RPP) was calculated. The first measurement was
performed 7 minutes after having a shower (5 minutes of rest in sitting position followed by 2
minutes of still standing), the second measurement was performed immediately after water
immersion (32.5 °C) up to the level of the heart, the third measurement after 2 minutes of
water immersion and the last measurement at the peak of work load during exercise therapy in
the swimming pool. Subjective perception of work load intensity was evaluated according to
Borg’s Rate of Perceived Exertion (8).
All the data were examined in the phase of clinical improvement of patients („on“ state)
without changes of regular anti-parkinsonian medication.
Kolmogorov-Smirnov test was used for normality verification, Pair T-test for dependent
samples to reveal changes caused by immersion into warm water (StatSoft, Inc., version 7).
The study was approved by the Ethical Committee of Medical Faculty, Masaryk University
and all participating patients signed their written consent.
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3
RESULTS
In comparison to the values of initial examination (standing out of water) there was a
significant decrease of values of heart rate and diastolic blood pressure in the second
examination performed immediately after water immersion. Systolic blood pressure did
not increase significantly. Rate x pressure product did not change significantly (Table 1).
Table1: Comparison of examination results before and immediately after water immersion
SBP DBP HR RPP
1st
measure-
ment
2nd
measure-
ment
1st
measure-
ment
2nd
measure-
ment
1st
measure-
ment
2nd
measure-
ment
1st
measure-
ment
2nd
measure-
ment
122±13 120±9 83±9 76±7 78±8 72±9 96±13 87±11
N.P. *p≤0.05 *p≤0.05 N.P.
Annotation: 1st
measurement before water immersion
2nd
measurement immediately after water immersion
The same trend was also present after 2 minutes of still standing in the swimming pool. In
comparison to the initial values (standing out of water) there was a highly significant
decrease of values of heart rate, diastolic blood pressure and rate x pressure product in the
third examination performed after 2 minutes of still standing in the swimming pool (Table
2).
Table 2: Comparison of examination results before water immersion and after 2 minutes of
still standing in the swimming pool
SBP DBP HR RPP
1st
measure-
ment
3rd
measure-
ment
1st
measure-
ment
3rd
measure-
ment
1st
measure-
ment
3rd
measure-
ment
1st
measure-
ment
3rd
measure-
ment
122±13 119±7 83±9 73±8 78±8 67±7 96±13 80±12
N.P. **p≤0.01 *p≤0.05 **p≤0.01
Annotation: 1. measurement before water immersion
3. measurement after 2 minutes of still standing in water
At the peak of exercise therapy work load there was a significant increase of systolic
blood pressure and rate x pressure product in comparison to the values of examination 3
performed after 2 minutes of still standing in the swimming pool (Table 3). The values of
109
4
diastolic blood pressure, heart rate and rate x pressure product approximated to the values
of initial examination in standing out of water (Table 4).
Table 3: Comparison of examination results after 2 minutes of water immersion and at the
peak of exercise therapy work load
SBP DBP HR RPP
3rd
measure-
ment
4th
measure-
ment
3rd
measure-
ment
4th
measure-
ment
3rd
measure-
ment
4th
measure-
ment
3rd
measure-
ment
4th
measure-
ment
119±7 129±7 73±8 80±7 67±7 75±12 80±12 97±18
*p≤0.05 N.P. N.P. *p≤0.05
Annotation: 3rd
measurement after 2 minutes of still standing in water
4th
measurement at the peak of exercise therapy work load
Table 4: Comparison of examination results before water immersion and at the peak of
exercise therapy work load
SBP DBP HR RPP
1st
measure-
ment
4th
measure-
ment
1st
measure-
ment
4th
measure-
ment
1st
measure-
ment
4th
measure-
ment
1st
measure-
ment
4th
measure-
ment
122±13 129±7 83±9 80±7 78±8 75±12 96±13 97±18
N.P. N.P. N.P. N.P.
Annotation: 1st
measurement before water immersion
4th
measurement at the peak of exercise therapy work load
The exercise therapy work load was evaluated with the use of Borg’s Rate of Perceived
Exertion. The rating fluctuated between 11 and 14 from the maximum of 20 in all
examined patients.
DISCUSSION
There is no agreement in opinions on the impact of water immersion on blood pressure.
We found scientific sources describing decrease of systolic and diastolic blood pressure in
110 5
thermo-neutral bath of 34-35°C (8) and hypo-thermal bath of 32°C (9) as well as sources
declaring mild increase of systolic blood pressure and no changes of diastolic blood
pressure in thermo-neutral (34.5°C) bath and decrease of diastolic blood pressure in hypothermal
bath of 30°C (10). Some studies found no changes of blood pressure during
thermo-neutral bath (11, 12).
In our group of examined PD patients we found statistically significant decrease of
diastolic blood pressure in thermo-neutral bath of 32.5°C. Systolic blood pressure
increased only in the course of exercise unit.
Water immersion in PD patients leads to decrease of resting heart rate known as diving
reflex. The intensity of sympathetic activity decrease and vagal activity increase depends
mainly on the depth and speed of immersion and on water temperature (11, 12). Intensive
reaction may cause extreme bradycardia and sudden death. (13). Activity of reninangiotensin
system also decreases (14, 9). In our group of PD patients the decrease of
heart rate was present immediately after water immersion and lasted during the course of
exercise therapy unit. The similar results were described by Fardy et al. (15) in the study
with healthy subjects.
No other clinically relevant negative aspects of PD exercise therapy in the swimming pool
were found during the course of 12 weeks of exercise therapy.
Regular controlled group or individual rehabilitation is recommended to the majority of PD
patients (5). Elderly patients can benefit from rehabilitation as well as younger subjects (6).
CONCLUSION
Thermo-neutral (32.5°C) water immersion and up to the level of heart caused statistically
significant decrease of heart rate and diastolic blood pressure in patients with Parkinson
disease. This trend lasted for the period of exercise therapy unit in the water. The increase
of systolic blood pressure and heart rate was detected only at the peak of exercise therapy
work load in water when the values approximated those of initial examination before
water immersion.
We have not observed any subjective inconveniences and any clinical manifestations of
possible haemodynamic pathological changes during exercise therapy in our study.
We consider group form of controlled hydro-kinesitherapy a suitable and safe supplement
to classic exercise therapy unit in the frame of neurorehabilitation.
111 6
Further research on a larger group of PD patients is necessary to prove the results of this
study.
Supported by MSM0021622402.
REFERENCES
1. Helly, M.A., Morris, J.G.L., Traficante, R., Reid, W.G.J. et al. The Sydney multicentre
study of Parkinson’s disease: Progression and mortality at 10 years. Journal of neurology,
Neurosurgery and Psychiatry, 1999, 67/3, p. 300-308. (fulltext)
2. Gorell, J.M., Johnson, C.C., Rybicki, B.A. Parkinson’s disease and its comorbid disorders:
An analysis of Michigan mortality data, 1970-1990. Neurology, 1994, 44, p. 1865-1868.
3. Ellis, T. et al. Efficacy of a physical therapy program in patients with Parkinson's
disease: A randomized controlled trial. Archives of Physical Medicine and Rehabilitation,
2005, 86/4, p. 626-632.
4. Cees, J.T. et al. The effects of physical therapy in Parkinson’s disease: a research
synthesis. Archives of Physical Medicine and Rehabilitation, 2001, 82/4, p. 509-515.
5. Lun, V. et al. Comparison of the effects of a self-supervised home exercise program
with a physiotherapist-supervised exercise program on the motor symptoms of Parkinson's
disease. Movement Disorders, 2005, 20/8, p. 971-975.
6. Reuter, I. Engelhardt, M. Exercise training and Parkinson’s disease. Placebo or
essential treatment?
The Physician and Sportsmedicine, 2002, 30/3, p. 43-50.
7. Borg, G. Psychophysical bases of perceived exertion. Med Sci Sports Exercise, 1982,
14, p. 377-381.
8. Henschel, H.D. Vergleichende Untersuchungen zur Behandlung mit
Kohlensaurenbader. Arch Phys Ther (Leipzig), 1962, 14, p. 327-334.
9. Šrámek, P., Šimečková, M., Janský, L. Human physiological responses to immersion
into water of different temperatures. Eur J. Physiol, 2000, 81 (5), p. 436 – 442.
10. Park, K.P., Choj, J.K., Park, Y.P. Cardiovascular regulation during water immersion.
Appl Human Sci, 1999, 18 (6), p. 233-241.
11. Mano, T., Iwase, P., Saito, M., et al.: Neural and humoral controlling mechanism of
cardiovascular functions in man under weightlessness simulated by water immersion.
Acta Astronaut 1991; 23: 31 – 33.
112
7
12. Miwa, C., Sugiyama,Y., Mono. T. et al. Spectral characteristics of heart rate and blood
pressure variabilities during head-out water immersion. Environ Med, 1966, 40 (1), p. 91 -
94.
13. Lin, Z.C. Applied physiology of diving. Sports Medicine, 1988, 5, p. 41 – 56.
14. Gabrielsen, A., Pump, B., Bie, P.et al. Atrial distension, haemodilution and acute
control of renin release during water immersion in humans.
Acta Physiol Scand, 2002, 174 (2), p. 91 -99.
15. Fardy, P.P., Franklin, B.A., Porcari, J.P., Verrill, D.E. Training techniques in cardiac
rehabilitation. Human Kinetics, 1998, p. 88-105.
113
1
PHYSIOTHERAPY AND CIRCADIAN BLOOD PRESSURE
VARIABILITY
Alena Havelková, Jarmila Siegelová, Bohumil Fišer,
Leona Mífková, Veronika Chludilová, Jaroslava Pochmonová,
Pavel Vank, Michal Pohanka, Jiří Dušek, Germaine Cornélissen*, Franz Halberg*
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine,
Masaryk University, St. Anna Teaching Hospital, Brno, CZ, *Halberg Chronobiology
Center, University in Minnesota, USA
INTRODUCTION
High blood pressure is number one in risk factors of cardiovascular diseases and
civilization diseases in general that are known as yet.
It seems that the repeated single measurements of blood pressure in the medical practice
is no longer sufficient for the determination of optimal treatment of patients with heart
diseases. Ambulatory monitoring of blood pressure opens new possibilities in
prevention, screening, diagnostics and therapy of chronically ill patients. Blood pressure
is a biological parameter showing, in spite of numerous regulation mechanisms,
considerable variability beat-to-beat, within 24 hours and also in longer time intervals
(weekly, monthly) (Siegelová et al. 1993, Siegelová and Fišer 2005, Homolka 2006).
24-hour monitoring contributed in recent years significantly to the progress in
diagnostics and therapy of cardiovascular diseases. In combination with the knowledge
of pharmacokinetics and pharmacodynamics of antihypertensive medicines it offers
other possibilities of medical treatment (Souček, Kára et al. 2002; Siegelová et al.
2004). A longer lasting (7 days at least) monitoring increases validity of obtained
information with observing biological rhythms of blood pressure. The knowledge of
chronobiology of circadian cycles of physiologic functions initiates a modern trend in
medicine, i.e. intervention before the manifestation of clinical symptoms of the disease
(Siegelová and Fišer 2005, Halberg et al. 2006, Watanabe et al. 2006).
114
2
Monitoring of blood pressure response to physical load is well-founded not only in
exercise diagnostics of hypertonic patients and of patients with cardiovascular and other
internal diseases, but also in setting up and checking an optimal training program that
should be beneficial to improvement or stabilization of their health state. Cardiovascular
rehabilitation is perceived as a process helping the patients with heart diseases in
retaining their optimal physical, mental, working and emotional state. Its principles are
based on the assumption that the adaptation of cardiovascular system to physical load is
conditioned by regular, particularly dynamic endurance activities of adequate kind and
intensity (Placheta et al. 1999).
PURPOSE
The objective of this study was to find if there is a relationship between the day time
when cardiovascular rehabilitation was running in the patients after myocardial
infarction and an average daily value of systolic and diastolic blood pressure at 7-day
ambulatory monitoring.
METHODS
The set being monitored consisted of ten patients after myocardial infarction of age
(63 ± 6.3) and ejection fraction (43 ± 12.3) %.
The patients underwent phase II of cardiovascular rehabilitation (controlled
ambulatory rehabilitation program) lasting two to three months with the frequency of
two times or three times in a week at the Department of Functional Diagnostics and
Rehabilitation of St. Anna Teaching Hospital.
In the course of rehabilitation they went through 7-day ambulatory monitoring of
blood pressure. During BP recording they did not interrupt their pharmacotherapy.
The seven-day blood pressure monitoring was made by using the instrument TM –
2421 of the Japanese firm AD on the principle of oscillometric analysis. During the time
of monitoring the patients carried the recording instrument in the case on the body and
115
3
cuff with the measuring probe above a. brachialis. The instrument measured blood
pressure for 7 days repeatedly every 30 minutes from 5 to 22 h and once in an hour
from 22 to 5 h. If a value that was not very probable from the point of view of the
setting-up of the instrument was recorded, another check measurement was made
(Siegelová et al. 2004).
The measured BP values for every patient from the monitored set were statistically
processed in the form of arithmetic means. The profiles of BP in the days without
cardiovascular rehabilitation (hereafter in the days without exercises) and in the days
with cardiovascular rehabilitation (hereafter in the days with exercises) in individual
time intervals were obtained as arithmetic mean of the values in every hour of
individual days with denying the individuality of persons in the monitored set.
The average SBP and DBP and their standard deviations (SD) in the given days were
determined by the calculation of arithmetic mean of these values. These average values
were compared by means of two-factor analysis of variance without repetition
(ANOVA). Concrete differences between the averages from the days without exercises
and the averages of the values in the time intervals when cardiovascular rehabilitation
was running in individual groups of patients, were tested by the paired t-test.
RESULTS
Table 1 gives the average of BP profiles in the days without exercises and with
exercises that were obtained from arithmetic means of SBP and DBP for every hour of
individual days regardless of individual differences between the patients in the
monitored set.
The calculated value F (ANOVA) for SBP highly exceeds the critical value for the
significance level α = 0.01. It was proved that there are statistically conclusive
differences between the daily averages of SBP in the monitored groups. The differences
of averages in individual groups of the days with exercises in comparison with the
group of days without exercises were tested by paired t-test.
The average value of SBP in 24 h in the group of patients doing exercises from 9 a.m.
to 10.15 a.m. is statistically highly conclusively higher (α = 0.01) in comparison with
116
4
the group of days without exercises (133 or 120 mm Hg). The average value of SBP in
24 h in the group of patients doing exercises from 1.30 p.m. to 2.45 p.m., however, is
statistically conclusively lower (α = 0.05) (115 or 120 mm Hg). The averages of the
remaining two groups and of the group without exercises are identical. It is interesting
that in all groups with exercises lower minimal values of SBP were found than in the
group without exercises.
The calculated value F (ANOVA) for DBP also highly exceeds the critical value for the
significance level α = 0.01. It was proved that there are statistically conclusive
differences between the averages of individual monitored groups. The results of paired
t-test demonstrate the statistically highly conclusively higher values in the groups of
days when the exercises were running from 7.30 a.m. to 8.45 a.m. and from 9 a.m. to
10.15 a.m. (α = 0.01) and statistically highly conclusively lower values in the group of
days when the patients were doing exercises in the afternoon from 1.30 p.m. to 2.45
p.m. (α = 0.01) in comparison with the average of values in 51 days without
cardiovascular rehabilitation (71, 75, 63 or 69 mm Hg).
Table 1: 24-hour profile of systolic and diastolic blood pressure [mm Hg]
obtained as arithmetic mean of values of the patients
without
exercises
with exercises time [h]
7:30-8:45 9:00-10:15 10:30-11:45 13:30-14:45
N 51 10 3 6 3
[mmHg] SBP DBP SBP DBP SBP DBP SBP DBP SBP DBP
x 120 69 120 71** 133** 75** 120 67 115* 63**
SD 5.9 4.0 11.9 5.6 12.0 10.2 12.9 6.3 12.8 6.3
xmax 128 75 152 83 158 91 142 81 136 74
xmin 110 62 99 62 108 57 97 56 94 48
tcalculated. 0.221 3.448 5.317 4.029 0 1.657 2.795 6.183
Fcalculated 16.371 23.662
117
5
n – number of monitored days
x - arithmetic mean SD – standard deviation
xmax , xmin - maximal and minimal average circadian value of blood pressure
‫٭‬ statistically conclusive difference at the significance level α = 0.05
‫٭٭‬ statistically conclusive difference at the significance level α = 0.01
t criterion of paired t-test t (0.05) = 2.068 t (0.01) = 2.807
F criterion of analysis of variance F (0.05) = 2.471 F (0.01) = 3.530
DISCUSSION
The diagnosis based on one clinical measurement of BP is wrong in about 40 % of
the cases compared to 24-hour ambulatory monitoring. The 48-hour record furthermore
reduces uncertainty in assessment of blood pressure parameters by 35 % in comparison
with 24-hour monitoring. Halberg et al. (2006) and Watanabe et al. (2006) tend to a
long-term monitoring of blood pressure for the sake of increasing validity of the
obtained data and optimization of the therapy. They recommend a 7-day recording of
blood pressure to cover the biological week.
The nature of the reaction of cardiovascular system to exercises depends on intensity,
type and duration of physical load and also on individual characteristics of organism
and on external influences. Even a moderate load affects tonus of vegetative nervous
system by reducing activity of n. vagus and stimulation of sympathicus occurs.
Autonomous nervous regulations with predomination of sympathicus at a high intensity
of the load bring about increasing of heart rate, peripheral resistance of vessels,
secretion of catecholamins and blood pressure. After the termination of the load
sympathetic activity decreases and parasympathetic activity increases with latency.
Systolic blood pressure at the dynamic load of low and moderate intensity quickly
achieves a steady state (130 – 170 mm Hg), diastolic pressure does not show substantial
changes or slightly decreases. The load of submaximal and maximal intensity leads to
gradual increasing of systolic pressure. Diastolic blood pressure is mostly decreasing,
but in some cases is also increasing. Both blood pressure parameters react to static
(isometric) load by increasing (Placheta et al. 2001).
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6
This study confirms the blood pressure reaction to the load, both in the interval of
proceeding exercises and in the whole circadian cycle. Systolic blood pressure was
increasing at the time of rehabilitation, sometimes, however, also within two hours after
the termination of exercises. The reaction of diastolic pressure at the load is less specific
in physiological conditions. Regularity in the curves of diastolic pressure in individual
persons being tested is also difficult to be found.
Both foreign literature and the studies carried out in St. Anna Teaching Hospital
prove positive influence of cardiovascular training on the prognosis of heart diseases.
Mífková et al. (2005) assess successfulness of the rehabilitation program depending on
how early rehabilitation is started (already during hospitalization), on the length of
duration of individual phases of the training, and on frequency of arranging individual
exercise units. The content of individual phases of the rehabilitation program was also a
subject of the discussion (Chaloupka et al. 2006, Mífková et al. 2006).
For example, according to Jančík (2005), it is not the time devoted to exercises or the
particular type of exercises, but intensity of the load that is decisive for a direct
influence on prognosis of cardiovascular diseases, without any regard to the type of
exercises being done by the patient.
This study adds to the above-mentioned facts, concerning cardiovascular
rehabilitation, the information that, apparently, the effect of the complex therapy of
heart diseases depends also on the time of day when the patients perform the
rehabilitation program.
The tested persons were divided in this study into four groups differing in time
intervals of rehabilitation. It was proved that the time of exercises influences the
average value of blood pressure during the circadian cycle. Cardiovascular training
taking place in the morning increased statistically conclusively the average 24-hour
value of blood pressure in comparison with the days without exercises. Exercises
arranged in the afternoon decreased statistically conclusively the average 24-hour value
of blood pressure
Influence of exercises on circadian variability of blood pressure was investigated also
by Homolka (2006); he states that the exercises of an aerobic nature done in the evening
by patients with hypertension caused abnormal fluctuation of circadian values of blood
pressure contributing to CHAT (Circadian-Hyper-Amplitude-Tension). He did not find
119
7
any abnormalities in the days without exercises and with exercises done in the morning
and in the afternoon. Effective complex therapy of high blood pressure and
cardiovascular rehabilitation as an integral part of it are a basic condition for the
decrease of morbidity and mortality caused by cardiovascular diseases and their
complications. Our studies show that the time of day when the load is applied influences
average 24-hour values of blood pressure.
CONCLUSION
It was proved that there is a statistically highly conclusive dependence of SBP and
DBP values on the day time when the patients went through cardiovascular
rehabilitation.
Supported by MSM0021622402
LITERATURE
1. Halberg, F., Cornélissen, G. & Schwartzkopff, O. (2006). Seven day blood pressure
measurement: Contraversion in single 24-h profiles of blood pressure and heart rate.
In Halberg, F., Kenner, T., Fišer, B., Siegelová, J. Noninvasive Methods in
Cardiology. s. 10 – 26.
2. Homolka, P. (2006). Cirkadiánní variabilita krevního tlaku u pacientů s esenciální
hypertenzí. Brno: LF MU. 149 s.
3. Chaloupka, V., Siegelová, J. & Špinarová, L. (2006). Rehabilitace nemocných
s kardiovaskulárním onemocněním. Cor Vasa, 48 (7 – 8).
4. Jančík, J. (2005). Rehabilitace po infarktu myokardu a revaskularizace u starších
nemocných. Vnitřní lékařství, 51 (4), s. 388 – 389.
5. Mífková, L., Kožantová, L. & Siegelová, J. (2005). Kombinovaný trénink u pacientů
po akutním infarktu myokardu. Medicina Sportiva Bohemica a Slovaca, 14 (3), s.
115 – 123.
120
8
6. Mífková, L., Siegelová, J. & Vymazalová, L. (2006). Intervalový a kontinuální
trénink v kardiovaskulární rehabilitaci. Vnitřní lékařství, 52 (1), s. 44 – 50.
7. Placheta, Z. (1999). Zátěžová diagnostika v ambulantní a klinické praxi. Praha:
Grada.
8. Siegelová, J. & Fišer, B. (2005). Diagnostika hypertenze – současnost a budoucnost.
Vnitřní lékařství, 51 (S 3), s. 50 – 53.
9. Siegelová, J., Fišer, B. & Dušek, J. (1993). 24-hodinové monitorování krevního
tlaku u nemocných s esenciální hypertenzí. Vnitřní lékařství, 39 (2), s. 183 – 190.
10. Siegelová, J., Fišer, B. & Dušek, J. (2004). Nové trendy v monitorování krevního
tlaku. Postgraduální medicína, 6 (5), s. 474 – 477.
11. Souček, M. (2002). Klinická patofyziologie hypertenze. Praha: Grada.
12. Watanabe, Y., Katinas, G. & Cornélissen, G. (2006). Time course of blood ressures
over 18 years analyzed separately by day and by week. In Halberg, F., Kenner, T.,
Fišer, B., Siegelová, J. Noninvasive Methods in Cardiology. s. 42 – 46.
SUMMARY
The objective of this study was to find if there is a relationship between the time
when cardiovascular rehabilitation was running in the patients after myocardial
infarction and an average daily value of systolic and diastolic blood pressure at 7-day
ambulatory blood pressure monitoring.
Systolic and diastolic pressure significantly increased in the patients who underwent
cardiovascular rehabilitation in the morning from 9.00 a.m. to 10.15 a.m., and it
significantly decreased in those who did their physical exercise in the afternoon from
1.30 p.m. to 2.45 p.m., compared to the blood pressure value in the days without
rehabilitation.
KEY WORDS
Blood pressure, ambulatory blood pressure monitoring, circadian variability,
chronobiology, cardiovascular rehabilitation.
121
FITNESS IN MULTIPLE SCLEROSIS
Lumír Konečný1
, Petr Pospíšil1
, Michal Dufek2
, Lenka Drlíková1
, Farag Hassan
Anbais1
, Ashref Ali Erajhi1
, Petr Dobšák1
,
Pavel Vank1
, Jarmila Siegelová1
1
Department of Functional Diagnostics and Rehabilitation and 2
1st
Neurological
Department, Faculty of Medicine, Masaryk University, St. Anna Teaching Hospital,
Brno, CZ
INTRODUCTION
Multiple sclerosis (MS) is chronic system auto-immune disease bringing about
functional neurological deficit on the basis of dissemination of demyelinisation focuses
in CNS area (1). At the beginning of the disease appears already also axon involvement
that is probably a cause of persisting neurological deficit. Maximum axon loss occurs in
the first years of the disease (period with minimal disability and clinical finding) and, as
a result of depletion of functional reserves of CNS, a substantial deceleration in
conduction of nerve impulse develops. Another axon loss brings on an irreversible
disability already (2). Demyelinisation and axon involvement are localized particularly
in periventricular area, in brain-stem, cerebellum, lateral and posterior cords of spinal
chord. Predominant manifestations include central pyramidal symptoms, cerebral, stem
and sensitive signs, disorders of autonomous regulation, continence, etc. (3). Multiple
sclerosis also attacks basic physiologic response to load by demyelisating processes (4,
5). Functional changes in skeletal musculature, particularly reduction of the number of
fibres of the type I, reduction of oxidative abilities and prevailing anaerobic activity of
skeletal extrafusal fibres (6) are ranked among other pathophysiological processes.
Increasing health troubles lead to secondary signs of physical decondition with a
gradual reduction of muscular mass, appearance of functional troubles and further
reduction of cardiorespiratory fitness (7). However, it is probably caused by
deconditioning in consequence of the lack of physical activities. The restriction of
122
physical activities in MS patients was confirmed (8). It could be primarily caused by
muscle weakness and fatigue (9). It is suggested that aerobic exercises and
strengthening may help to prevent secondary changes partially caused by
deconditioning (10). Controlled exercising activity represents a significant element
influencing physical decondition and course of MS disease (4, 11, 12, 13, 14).
Assessment of functional condition of cardiorespiratory and metabolic activity and of
determination of functional reserves could help to set up optimal individual
rehabilitation workload with an adequate intensity (11, 12, 13, 14, 15).
PURPOSE
The study was aimed to analyse physical fitness, metabolic and hemodynamic
functions in the set of patients with MS and comparison of the measured results with
actual standards, investigation of fatigue and independence.
METHODOLOGY
The examined set consisted of patients from neurological outpatient clinic for MS of
1st
Neurological Department, St. Anna Teaching Hospital and patients in Brno-town.
The patients were tested in the clinically stabilized disease condition. They confirmed
by signature of “Informed approval of the patient” their participation in the study. The
study was approved by appropriate ethical commission of St. Anna Teaching Hospital
in Brno. Evaluation of clinical disability, independence and fatigue was carried out
before the exercise examination.
Exclusion criteria of contraindications for going through spiroergometry and ability of
the patient to undergo the examination on bicycle ergometer were the criteria for
inclusion. The patients with internal, metabolic and other diseases, which could
influence validity of the exercise test results, were excluded.
We use following tests for clinical functional impairment:
EDSS (Kurtzke’s Expanded Disability Status Scale) (16) is a standard scale for
evaluation of clinical disability in patients with MS. It is a neurological examination
with evaluation by 0.5 point, in interval from 0 (no functional disorder or impairment)
to 10 (death due to MS), MS impact on 8 basic functional systems.
123
FIM (Functional Independence Measure) (17) is a scale for evaluation of
independence in basic daily activities. Evaluation applies to locomotive skills, mental
functions, and general degree of independence. Possible range is 18 – 126 points.
MFIS (Modified Fatigue Impact Scale) (18) is a questionnaire including subjective
assessment of fatigue impact on physical condition (MFISp), cognitive (MFISc) and
psychosocial functions (MFISps). It contains 21 questions with evaluation of 0 – 4
points (0 – on fatigue impact on the function; 4 – almost permanent fatigue impact).
Possible range is 0 to 84 points.
Examinations of physical fitness and oxygen transport system:
Symtom limited spiroergometry was carried out in standard conditions (15) on
bicycle ergometer (system for the analysis of respiratory gases, MedGraphics, USA).
The load was measured out in 2 min intervals by 20 W. The examination determined
functional parameters: peak work capacity (Wpeak), peak work capacity per kg of body
mass (Wpeak. kg-1
), peak oxygen consumption (VO2peak), peak oxygen consumption per
kg of body mass (VO2peak . kg-1
), pulse oxygen (VO2 . SF-1
), minute ventilation (VE),
relative ventilation (VE . kg-1
). Then resting and highest achieved values of systolic
pressure (SBPrest and SBPpeak) and diastolic pressure (DBPrest and DBPpeak), and resting
and highest achieved values of heart rate (HRrest and HRpeak) were recorded. The
resulting values were mathematically processed and compared with actual standards
IBP for Czechoslovak healthy population (International Biologic Program, 1977) (19).
Statistical data analysis (program STATISTICA for Windows - ver.7.7) was carried out
by means of Wilcoxon test for non-paired values and correlation analysis (Spearman, r,
P < 0.05) of individual parameters.
RESULTS
35 patients with diagnosed MS disease were examined - 28 women (80 %) and 7
men (20 %) of mean age 49.1 ± 10 years. The degree of disability according to EDSS
was 3.0 ± 1.2 (medium degree of disability). In 17 patients we found a relapse-remittent
(RR) form of the disease, in 16 patients a secondarily progressive (SP) and in 2 patients
a primarily progressive (PP) form of the disease. In the questionnaire MFIS the patients
assessed their fatigue on average as moderate to medium, with an approximately
identical influence of physical and cognitive decondition. Independence, tested by the
124
scale FIM, achieved the upper limit of the scale range, i.e. minimal limitation of
independence in doing common daily activities. General characteristic of the set and
evaluation of the disease activity are given in Table 1.
Table 1 Basic anthropometric data and data defining MS disease in the set being
examined (the values are expressed as mean ± SD)
Achieved value
Min. and max.
values
Clinical disablility (EDSS) 3.0 ± 1.2 0 - 10
Fatigue (MFIS) 32.3 ± 17.9 0 - 84
MFISp – physical 16.8 ± 8.9 0 - 36
MFISc – cognitive 12.7 ± 8.4 0 -40
MFISps – psychosocial 2.7 ± 2.3 0 - 8
Independence (FIM) 116.3 ± 10.9 18 - 126
Body mass index (BMI) 24.7 ± 4.6
Length of disease MS (years) 15.4 ± 12.5
Age (years) 49.1 ± 10.0
Parameters of physical fitness and metabolic functions
Statistical evaluation of mean values found in examinations indicated a significant
decrease of most parameters of functional fitness in patients from the monitored set in
comparison with actual IBP standards. The given finding demonstrates a significantly
lower functional fitness in MS patients. A detailed survey of the results and statistical
evaluation is in Table 2.
Table 2 Measured values of spiroergometric parameters in comparison with the Czech
IBP standard (the values are expressed as mean ± SD)
Spiroergometric Measured Value according to
parameters value IBP standard
Statistical
significanc
e
Wpeak (W) 89.0 ± 34.1 176.3 ± 28.4 ***
Wpeak. kg-1
(W . kg-1
) 1.29 ± 0.4 2.5 ± 0.3 ***
HRpeak 140,8 ± 23,8 177.7 ± 7.5 ***
125
VO2peak (ml O2) 1432.9 ± 474.4 2021.1 ± 320.4 ***
VO2peak . kg-1
(ml O2) 20.6 ± 5.9 28.5 ± 3.2 ***
VO2peak . SF-1
(ml.tep-1
) 9.9 ± 3.0 11.4 ± 0,02 *
VE (L.min-1
) 44,9 ± 18,6 78.3 ± 12.5 ***
VE.kg-1
(L.min-1
.kg-1
) 0.7 ± 0.3 1.11 ± 0.14 ***
RER 1.0 ± 0.1 1.1 ± 1.8 **
* P < 0.05 ** P < 0.001 *** P < 0.0001
Hemodynamic parameters
Average resting values of systolic blood pressure at rest (SBPrest) were 125.4 ± 15.1
mmHg, of diastolic blood pressure at rest (DBPrest) 82.3 ± 9.1 mmHg and heart rate at
rest (HRrest) 72.8 ± 12.6 pulses.min-1
. The following factors participated in termination
of the exercise test: suddenly appearing total fatigue, probably due to MS (36 %),
fatigue of musculature of lower extremities (48 %), and achieving of hypertonic
reaction of BP (16 %). Statistical evaluation showed, however, significantly lower
values of peak heart rate at the lower achieved maximum performance and significantly
higher values of DBPmax (97.2 ± 21.4 mmHg) at the peak of the load in comparison
with actual Czech standards IBP. As to SBPmax values, no statistical significance was
proved. A rather low value of HRmax and increased values of DBPmax could indicate a
decreased level of physical performance and pathological (hypertonic) reaction of DBP
as a response of organism to physical loading by a dynamic form. Decrease of SBP in
the restitution phase showed normal values on average. Survey of the results is in Table
3.
Table 3 Measured values of hemodynamic parameters in comparison with Czech IBP
standards (the values are expressed as mean ± SD)
Hemodynamic Measured Value according to
parameters Value IBP standard
P level
(Wilcoxon)
SBPmax (mmHg) 186.0 ± 27.7 177.9 ± 8.0 NS
DBPmax (mmHg) 97.2 ± 21.4 77.5 ± 8.6 ***
HRmax (pulse.min-1) 140,8 ± 23,8 177.7 ± 7.5 ***
* P < 0.05 ** P < 0.001 *** P < 0.0001
126
After statistical evaluation correlation analyses between neurological impairment
(EDSS), MFISp, FIM and parameters of functional fitness and metabolic functions were
carried out. General results of the analysis are in Table 4. The most important relation
was found between spiroergometric parameters and EDSS, and then in the subscale
MFISp. The assumption of the close relation between the scales FIM and MFIS has
been proved (r = -0.56, P < 0.001). In our set we have not found any relation between
FIM and EDSS (r = -0.05, NS), between EDSS and MFIS (r = 0.28, NS), we have only
found a small dependence between EDSS and the length of the disease (r = 0.35, P
<0.01). All correlation analyses were carried out, however, on a statistically small
sample of patients.
Table 4 Correlation between parameters of the spiroergometry and selected clinical
parameters (the values are given as Spearman coefficient r),
Length of EDSS MFIS MFISp FIM
the disease
Wpeak (W) -0,30 *** -0,67 * -0,41 ** -0,50 0,08
Wpeak. kg-1
(W . kg-1
) -0,27 *** -0,58 * -0,42 ** -0,49 0,10
HRpeak * -0,37 ** -0,48 * -0,39 * -0,38 0,08
VO2peak (ml O2) -0,24 ** -0,64 ** -0,43 ** -0,56 0,12
VO2peak . kg-1
(ml O2) -0,15 ** -0,47 * -0,38 ** -0,48 0,13
VO2peak . SF-1
(ml.tep-1
) -0,10 ** -0,48 -0,14 -0,31 -0,11
VE (L.min-1
) -0,32 ** -0,48 * -0,41 ** -0,51 0,12
VE.kg-1
(L.min-1
.kg-1
) -0,21 * -0,36 * -0,42 ** -0,49 0,20
* P < 0.05 ** P < 0.01 *** P < 0.001
DISCUSSION
A significant decrease of parameters of cardiorespiratory fitness in comparison with
normal population is documented in a number of studies (4, 11, 12, 13, 20, 21). Many of
them are resumed in the study of Motl et al. (22). As to the Czech studies published in
the world, especially the study of Řasová et al. (23) presents comprehensive results of
spiroergometric measurements made on the sample of 112 patients with MS; in the
majority of the cases we are in accordance with the results and conclusions of this
study. The results of our measurement represent the choice of the population of MS
127
patients with quite a low degree of subjectively perceived fatigue (MFIS 32.3 ± 17.9), a
high degree of independence (FIM 116.3 ± 10.9, 74 % of patients did not use any aids to
locomotion), and a relatively low degree of EDSS (3.0 ± 1.2) (24). The results of our
study showed a statistically very significant limitation of functional capacity of
cardiorespiratory system and physical fitness in comparison with actual standards
applicable to Czechoslovak population (19). The patients in the set with MS manifested
a rather low tolerance of dynamic load and a quite a low ability of achieving maximal
values of physical performance (23, 21). This fact also corroborates a preliminary
termination of the test. It can be explained by the block of conduction of nerve impulses
increasing with the increasing load (2, 21). Under the load two patients suffered heart
rhythm disorders that were not too grave and were not the reason for interrupting the
test. The pressure reaction of the examined set to the dynamic load showed hypertonic
reaction DBPmax at the load peak. This reaction can be explained by a higher vascular
resistance and a lower vascular elasticity in consequence of the long-time physical
inactivity and by a higher mean age of the set (15). Our results also imply the
correlation between the degree of neurological impairment (EDSS), MFISp and
spiroergometric parameters. The achieved results are limited by the size of the set. New
rehabilitation methods demonstrate decreasing fatigue (MFIS) and reduction of clinical
impairment (EDSS) on the basis of increasing cardiorespiratory fitness (4,11,12).
According to Zálišová et al. (25) physical condition and fatigue can be influenced by
suitably chosen rehabilitation and fatigue should not be taken as the load limit. The
results of the exercise test therefore represent, last but not least, a significant
contribution to the prediction of the load measured out optimally, mainly objectively
and relevantly, in rehabilitation programs for MS patients with quite a low degree of
clinical impairment.
CONCLUSION
The results of spiroergometry showed that in the examined set of MS patients there is
a very low tolerance of physical load and a rather low capacity of the transport system.
The study demonstrates the correlation between the results of the spiroergometry and
128
clinical functional impairment according to EDSS and fatigue according to MFIS
questionnaire.
Supported by MSM0021622402.
LITERATURE
1. HAVRDOVÁ, E. (2002). Roztroušená skleróza. Praha: Triton, 3.vyd. 110s., ISBN
80-7254-280-X.
2. HAVRDOVÁ, E. (2004). Význam včasné léčby roztroušené sklerózy mozkomíšní.
Neurologie pro praxi; č.5, s. 291-294.
3. BAREŠ, M. (2002) Evokované potenciály v diagnostice roztroušené sklerózy
mozkomíšní. Neurologie pro praxi č. 5, s. 244 – 248.
4. MOSTERT, S., KESSELRING, J. (2002) Effects of a short-term exercise training
program on aerobic fitness, fatigue, health perception and activity level of subjects
with multiple sclerosis. Multiple Sclerosis; 8(2):161-68.
5. PONICHTERA-MULCARE JA. (1993) Exercise and multiple sclerosis. Med Sci
Sports Exerc; 25: 451/65.
6. DE HAAN, A. (2000) Contractile properties and fatigue of quadriceps muscles in
multiple sclerosis. Muscle Nerve; 23:1534-41.
7. TANTUCCI C., MASSUCCI M. et al. (1996) Energy cost of exercise in multiple
sclerosis patients with low degree of disability. Mult Scler; 2: 161/67.
8. ALEXANDER V., KENT-BRAUN JA. (1997) Quantitation of lower physical
activity in persons with multiple sclerosis. Med Sci Sports Exerc: 517/23.
9. FISK JD., PONTEFRACT A. (1994) The impact of fatigue on patient with MS. Can
J Neurol Sci: 21: 9/14.
10. KENT-BRAUN J, SHARMA KR. et al. (1994) Effect of exercise on muscle
activation and metabolism in MS. Muscle & Nerve 17: 1162/69.
11. PETAJAN, JH., GAPPMAIER, E., WHITE, AT. (1996). Impact of aerobic training
on fitness and quality of life in multiple sclerosis. Ann Neurol; 39(4):432-41.
129
12. ROMBERG, A., VIRTANEN, A. (2004). Exercise capacity, disability and leisure
physical activity of subjects with multiple sclerosis. Mult. Sclerosis; 10(2):212-18.
13. SCHAPIRO RT, PETAJAN JH et al. (1988) Role of cardiovascular fitness in
multiple sclerosis: A pilot study. J Neuro Rehab 2: 43/49.
14. ZÁLIŠOVÁ K, HAVRDOVÁ E. (2001) Effect of aerobic load and rehabilitation on
patients with multiple sclerosis - pilot study. Multiple Sclerosis-Clinical and
Laboratory Research 7: 116.
15. PLACHETA, Z., SIEGELOVÁ, J. (1999). Zátěžová diagnostika v ambulantní a
klinické praxi, Praha: Grada, 1. vyd., 286 s., ISBN 80-7169-271-9
16. KURTZKE, J. (1983). Rating neurologic impairment in multiple sclerosis: an
expanded disability status scale (EDSS). Neurology, č. 33, s. 1444 – 1452.
17. VAŇÁSKOVÁ, E. (2004). Testování v rehabilitační praxi - cévní mozkové příhody.
NCO NZO, vyd. 1., 65 str. TZ 57-852-04
18. Multiple Sclerosis Council for Clinical Practice Guidelines (1998). Fatigue and
multiple sclerosis. Washington DC: Paralyzed Veterans of America.
19. SELIGER, V., BARTŮNĚK, Z., ROTH, Z. (1977). Metody a výsledky celostátního
výzkumu fysické zdatnosti obyvatelstva. Praha: Karolinum.
20. FOGLIO K, CLINI E. et al. (1994) Respiratory muscle function and exercise
capacity in MS. European Resp Journal 7: 23/28.
21. PONICHTERA-MULCARE JA, MAHEWS T. et al. (1995) Maximal aerobic
exercise of individuals with multiple sclerosis using three modes of ergometry.
Clincal Kinesiology 49: 4/13.
22. MOTL, RW, MCAULEY. E., (2005). Physical activity and multiple sclerosis: a
meta-analysis. Multiple sclerosis, II, 459-463.
23. ŘASOVÁ, K., BRANDEJSKÝ, P., HAVRDOVÁ, E. (2005). Spiroergometric and
spirometric parameters in patients with multiple sclerosis. Multiple Sclerosis; 11:
213-221.
24. VALACHOVIČOVÁ I. (2001). Návrh metodického postupu rehabilitácie u
pacientov s diagnózou sclerosis multiplex. Rehabilitácia; 34:199-203.
25. ZÁLIŠOVÁ, K. (2001). Effect of aerobic exercises applied in the frame of complex
physiotherapeutic program on fatigue in multiple sclerosis. In Rehabilitácia, roč.
2001, č.34 (4), s. 229-231.
130
SUMMARY
The aim of this study was to analyze the physical fitness, the functional parameters,
fatigue and independence in a group of patients with multiple sclerosis (MS), and to
compare the measured results with applicable standards.
Patients and methods: We examined 35 MS patients with clinically active form of MS
(age 49.1 ± 10.0 years, 28 women, 7 men, mean duration of MS 15.4 ± 12.5 years,
EDSS 3.0 ± 1.2) who participated in spiroergometric examination. All the patients
underwent a symptom-limited spiroergometry on bicycle (load 20 W increasing every 2
min) in order to evaluate the following parameters of functional capacity: maximal
oxygen comsumption (O2peak -ml O2,VO2peak.kg-1
, -ml O2 . kg-1
), maximal work load
(Wpeak -watts, Wpeak .kg-1 -
watts.kg-1
). We measured hemodynamic parameters – heart
rate (HR) and blood pressure (SBP and DBP). The registered data were compared with
Czech standards (IBP standards – International Biologic Program, Seliger et al., 1977).
The patients were also tested for fatigue (questionnaire MFIS) and functional
independence measure (FIM).
Results: The results showed a significant reduction of functional capacity, namely
in the values of parameters of spiroergometry (P<0.05, Wilcoxon paired) VO2peak
(1432.9 ± 474.4 ml O2), VO2peak.kg-1
(20.6 ± 5.9 ml O2.kg-1
), Wpeak (89.0 ± 34.1 watts)
and Wpeak .kg-
1 (1.29 ± 0.4 watts.kg-1
) at the exercise peak. Correlations between clinical
testing (EDSS), fatigue (MFIS) and spiroergometric data (Spearman coefficient) were
obtained.
Conclusions: The examined patients with MS have a low exercise tolerance and a
rather low capacity of the transport system. Spiroergometric parameters depend on the
degree of clinical disability and subjectively evaluated fatigue.
* * *
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1
PHYSIOTHERAPY LASTING THREE MONTHS IN PATIENTS
AFTER STROKE
Barbora Bártlová, Eva Nosavcovová, Marcela Nováková, Lenka Drlíková,
Abdul Karim Al Fadhli, Farag Hassan Anbais, Ashref Ali Erajhi, Leona Dunklerová,
Jarmila Siegelová
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine,
Masaryk University, Brno
INTRODUCTION
At present there are living in the Czech Republic almost 1,4 million citizens at the
age of 65 years and older than 65 years (i.e. 13.6 % citizens of the Czech Republic).
More than 18 % of the citizens are older than 60 years and 2.5 % of them are older than
80 years. Among the causes of morbidity in old age the cardiovascular system diseases
are number one, whereas strokes are the third most frequent cause of death. In our
country there is still one of the highest numbers of stroke in the world. The annual
incidence of ischemic ictus is in the range of 550 – 570/100 000 citizens in our country,
the annual ischemic ictus mortality is 70 – 80/100 000 citizens. With regard to the fact
that the phenomenon “ageing of old population” appears in all EU countries and that
atherosclerosis is present in 90 % people over 75, further considerable increase of these
figures can be expected (1,8,11,13).
AIM OF THE STUDY
The aim of our study was to evaluate the results of subsequent physiotherapy and
ergotherapy in 65 patients with diagnosis I60 – I69, in general affection of central
nervous system on the basis of vascular disease with motor activity disorder and
cognitive functions, and evaluation of independence measure in basic daily activities by
132
2
means of the test of functional examination (Functional Impairment Measure, FIM) and
Barthel test (BT).
SET OF EXAMINED PATIENTS
In 2005 we had 1064 treated 205 patients who were hospitalized in the unit of long
lasting physiotherapy. These patients with diagnosis I 60 – 69 had CNS affection on the
basis of vascular disease with motor activity disorder. Individual physiotherapy and
ergotherapy was prescribed to these patients.
After three months of therapy, the patients were discharged:
43 of them were discharged to home care ………………………………. 62 %
22 of them were discharged to social service institutions…….………….. 31 %
5 of them were moved to emergency ward ………………..………….….. 7 %
FIM test and BT were evaluated in 65 patients from the total number of 70, who
completed the physiotherapy and ergotherapy and were discharged to home care or to
institutions for social services. In five patients who were moved to emergency ward
these programs were not finished, and that is why this group was excluded from further
processing.
The average age of these patients was 71 years and median age was 74 years. The
average age of the patients discharged to home care was 72 years and that of the patients
discharged to social service institutions was 68 years. The age distribution of all 65
patients can be seen in graph 1.
Graph 1. The age distribution of 65 patients with stroke
10
9
5
12
16
12
1
0
2
4
6
8
10
12
14
16
< 60
60 - 64
65 - 69
70 - 74
75 - 79
80 - 84
85 - 89
133
3
Duration of physiotherapy and ergotherapy in our ward on average was 56 days,
intensity of rehabilitation was 1 hour of individual physiotherapy and half an hour of
ergotherapy 5 days in a week.
Graph 2. Duration of hospitalization in patients with stroke
METHODOLOGY
We used for our purposes FIM test and Barthel test evaluating independence in basic
everyday activities and are therefore suitable for monitoring of progress of the treatment
and therapeutic procedures.
FIM test – or measurement of functional independence, evaluates 18 activities in 6
categories: 1. Self attendance, 2. Control of sphincters, 3. Displacements, 4. Mobility, 5.
Communication, 6. Social abilities. Each item has a scale consisting of seven points,
when 1 means full assistance and 7 full independence. The total score can be 18 – 126
points (2,5,6,7,10).
Barthel test – test of basic everyday activities evaluates 10 activities:
1. Eating, drinking,
2. Dressing,
3. Taking a bath,
4. Personal hygiene,
5. Incontinence of defecation,
6. Incontinence of urination,
7. Ability to Use WC,
2
14 14
10
13
5
4
3
0
2
4
6
8
10
12
14
16
< 15
15 - 29
30 - 44
45 - 59
60 - 74
75 - 89
90 - 104
> 105
134
4
8. Displacement from the bed to the chair,
9. Walking on even ground,
10. Climbing stairs.
Individual items are evaluated either in three degrees of dependence – does not
accomplish (0), accomplishes with assistance (5) and accomplishes independently
without assistance (10), or in two degrees of dependence – does not accomplish (0),
accomplishes independently or with assistance (5), or in four specific degrees according
to circumstances (0,5,10,15). The total score can be therefore 0 – 100 points (2, 3, 4, 6,
12, 13).
As Barthel test does not contain evaluation of cognitive components, we used only
the evaluation of motor function score of FIM test to compare the results with FIM test.
RESULTS
We compared the results of motor score of FIM test and the results of Barthel test at
the beginning of rehabilitation and at then discharge in the whole set of 65 patients, and
then separately in the subgroup of 43 patients who were discharged home and 22
patients discharged to social service institutions.
FIM input FIM output Barthel input Barthel output
Means of the whole set 46±23 58±24** 42±30 55±30**
Discharged home 54±21 67±19* 53±28 67±24*
Discharged to social service
institutions
31±17 40±23* 22±22 32±27*
* p < 0,05, ** p < 0,01
For evaluation of functional state of input and output parameters of both tests we
used Wilcoxon paired test and the results showed statistically significant improvement
of the function at the level p < 0.01 in both functional tests in all groups.
Input and output results of both tests can be seen in graphs 3 and 4.
135
5
Graph 3. Results of functional state (FIM test) before and after 3-month rehabilitation
of patients with stroke
Graph 4. Results of functional state (BT) before and after 3-month rehabilitation of
patients with stroke
FIM
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80 90 100
ENTRANCE
DISCHARGE
BARTHEL TEST
0
20
40
60
80
100
120
0 20 40 60 80 100 120
ENTRENCE
DISCHARGE
136
6
DISCUSSION
The measured results show that a long-term rehabilitation of patients with stroke
leads to a substantial improvement of their independence in basic daily activities, which
eases their re-integration into normal life. These people can then leave the hospital and
go home. If their functional limitation does not allow it and they must go to a social
service institution, any improvement of their self attendance needs the help of the staff
nursing.
Expectations after stroke vary. Some patients die in spite of all possible care, the
least affected patients return to their original health state in the course of several hours
or days. Then, however, there are many patients who will have some sequential
problems. Here different tests of basic everyday activities can be applied in a large
extent, both as indicators of the rehabilitation progress, and as an advice to a
problematic part of self attendance, necessity of prescribing compensatory aids or
adjustment of the flat (9, 11, 13).
CONCLUSION
By means of functional tests (BT and FIM test) we demonstrated successfulness of
three-months rehabilitation in patients after CMP. Physiotherapy and ergotherapy are
indicated in all patients, regardless of the measure of functional impairment.
Supported by MSM0021622402
LITERATURE
1. Beneš, Vl. (2003). Ischemie mozku. Praha: Galén.
2. Grünerová, M. (2005). Neurorehabilitace. Praha: Galén.
3. Guth, A. (1995). Vyšetrovacie a liečebné metodiky pre fyzioterapeutov. Bratislava:
LIEČREH
4. Kalvach, P. (1997). Mozkové ischemie a hemoragie. Praha: Grada.
137
7
5. Kelly, P.J., Stein, J., Shafqat, S., Eskey, C., Doherty, D., Chang, Y., Kurina, A., and
Furie, K.L. (2001). Functional Recovery After Rehabilitation for Cerebral Stroke,
Feb 2001; 32: 530 - 534.
6. Kwon, S., Hartzema, A.G., Duncan, P.W., Min-Lai, S. (2004). Disability Measures
in Stroke: Relationship Among the Barthel Index, the Functional Independence
Measure, and the Modified Rankin Scale Stroke, Apr 2004; 35: 918 - 923.
7. Malý, M. (2001). Testovanie funkčnej sebestačnosti. Rehabilitácia, 34,2001 Med J
Aust; 177(8):452 – 456.
8. Nebudová, J. (1998). Cévní mozkové příhody – minimum pro praxi. Praha: Triton.
9. Országh, J., Káš, Sv. (1995). Cévní příhody mozkové. Praha: Brána.
10. Švestková, O. (2004). Možnosti posouzení funkčních schopností, aktivit
a participací. Autoreferát doktorandské práce. Praha: Univerzita Karlova.
11. Tarasová, M., Ošmerová, J., Svoboda, L., Vohlídalová, I., Vank, P., Frajhi, F.A.,
Karim, A.F.A., Sosíková, M., Siegelová, J. (2005). Testování funkčního stavu
pacientů po cévní mozkové příhodě. Hradec Králové: Univerzita Hradec Králové
12. Vaňásková, E. (2004). Testování v rehabilitační praxi – cévní mozkové příhody.
Brno: NCONZO.
13. Weber, P. (2000). Minimum z klinické gerontologie. Brno: IDVPZ.
SUMMARY
FUNCTIONAL RESULTS OF REHABILITATION LASTING THREE
MONTHS IN PATIENTS AFTER STROKE
The aim of this study was to evaluate the questionnaire Functional Impairment Measure
(FIM) and Barthel test in patients after stroke before and after three months of
rehabilitation and ergotherapy.
Methods: We examined 65 patients after stroke by means of questionnaire FIM and
Barthel test.
Results and conclusion: We have found after rehabilitation and ergotherapy by means of
FIM and Barthel test improvement of functional state in our patients. Rehabilitation and
138
8
ergotherapy are indicated in all patients with stroke without any regard to functional
state.
Key words: stroke, quality of life, rehabilitation, functional impairment measurement
139
EXERCISE TRAINING IN OBESE PATIENTS WITH CHRONIC ISCHEMIC
HEART DISEASE
Jaroslava Pochmonová, Leona Mífková, Veronika Chludilová, Hana Svačinová,
Pavel Vank, Michal Pohanka, Nabil Abdulah Ibrahim Al-Mahmodi,
Mohsin Kaid Ali Hashim, Abdul Karim Al Fadhli, Farag Hassan Anbais,
Ashref Ali Erajhi, Petr Pospíšil, Lumír Konečný, Jarmila Siegelová
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine,
Masaryk University, St. Anna Teaching Hospital, Brno, CZ
INTRODUCTION
Physiotherapy in patients with chronic ischemic heart disease is an essential part of
the treatment (1, 2, 3, 4, 5). Some patients, in addition to ischemic heart disease, are also
obese and their habitual exercise activity can be lower than in patients without obesity.
To indicate properly the exercise treatment in patients with ischemic heart disease with
obesity, we have studied the physical performance at the maximum symptom-limited
load in patients with chronic ischemic heart disease and obesity.
AIMS OF THE STUDY
The study was aimed at evaluation of twelve-week combined training on physical
performance (expressed as maximal achieved performance and performance converted
to 1 kg of the body mass), on indicators of capacity of the transport system (expressed
as maximal oxygen intake) and on quality of life in patients with ischemic heart disease
with regard to their body mass and possible obesity.
140
METHODOLOGY
The set of 88 examined patients with chronic ischemic heart disease was divided into
three groups according to the value of BMI. The first group included patients with BMI
up to 25, in the second group with BMI 25.1 – 30 and in the third group with BMI over
30; basic characteristics of the set are given in Tables 1 - 3.
Table 1. Basic characteristic of the group of patients with BMI up to 25
Table 2. Basic characteristic of the group of patients with BMI 25,1 - 30
Table 3. Basic characteristic of the group of patients with BMI over 30
The patients put on exercise therapy for ischemic heart disease had to comply with
the following criteria: they did not suffer acute myocardiac infarction or attack of nonstable
angina pectoris in the period of three months before starting the exercises, no
patient had any valvular defect or heart failure and treated hypertension.
The patients with serious dysrhythmia, with signs of hemodynamic instability, with
severe ischemiaof left ventricul at rest or under load were excluded. The patients with
Number (n) 16
Age (years) 60.9±8.9
EF (%) 47.7±12.6
BMI (kg.m2
) 23.9±1.2
Number (n) 50
Age (years) 63.0±9.6
EF (%) 49.0±9.5
BMI (kg.m2
) 27.3±1.6
Number (n) 22
Age (years) 62.4±10.8
EF (%) 48.9±9.7
BMI (kg.m2
) 31.9±2.6
141
uncontrolled hypertension and diseases ruling out exercise therapy also were not
included into the set.
Examinations made within the framework of this study. Before starting exercise
therapy all patients were submitted to entrance examination of symptom-limited
spiroergometry. In addition to the basic clinical examination (to exclude
contraindications of the load examination) their ejection fraction of left ventricle was
determined by Doppler echocardiography with the instrument SONOS 5500 (Hewlett
Packard).
Evaluation of the transport system function was realized by means of spiroergometric
load test on bicycle ergometer. The twelve-lead electrocardiogram was recorded by the
instrument Cardiovit CS 100 – Schiller. Ventilation-respiration values were determined
by gas analyzer Pulmonary Function System 1 070 – MedGraphics CPX/D, USA,
equipped with software for their analysis and evaluation.
The examination was carried out in morning hours and the patients were noticed in
advance that they should take the morning dose of their usual medication. Each patient
was given the reason of examination and expected results. From the beginning of the
load test twelve-lead EKG at rest was monitored. In the course of 2 to 5-minute phase of
adaptation sitting on the ergometer because of stabilizing the parameters, rest values of
heart rate (HR) and blood pressure (BP) were read.
The protocol with progressive load without interruptions up to the symptom-limited
maximum was determined for the examination (6). ECG record was taken and the
examined patient assessed his subjective perception of the load intensity (rating of
perceived exertion - RPE) and his blood pressure (BP) was measured by auscultation
method by means of a mercury manometer. Respiratory parameters in exhaled air ware
determined by means of a breath gas analyser in real time breath-to-breath. On the basis
of the measured values the arithmetic mean was calculated for every 30 seconds of load.
Seattle Angina Questionnaire. At the beginning and after the completion of the
rehabilitation program the patients were given Seattle Angina Questionnaire (SAQ) to
be filled out for finding out their subjective perception of health state and quality of life.
The questionnaire is divided into five sections (further and in the results SAQ 1-5) and
contains nineteen items altogether (7, 8, 9, 10).
142
Section 1 (SAQ 1) The patient indicates how the chest pain or anginous pain during
the last four weeks restricted him in performing activities given in the section. The
activities are arranged according to their physical strenuousness.
Section 2 (SAQ 2) It deals with comparison of the present health state with the
period four weeks ago as to the frequency of anginous troubles in performing routine
daily activities.
Section 3 (SAQ 3) The patient indicates how many times a day or a week he had
anginous troubles in the last month in comparison with the same period four weeks ago
and how many times he had to take nitroglycerin because of them.
Section 4 (SAQ 4) It concerns subjective perception of the treatment and satisfaction
of the patient with it.
Section 5 (SAQ 5) The last part should convey how the patients perceive quality of
their life with the disease and its possible fatal end.
The study was approved by local ethical committee and the patients signed their
informed approval.
The results were presented as average ± standard deviation, statistical evaluation was
made by using Student T-test and Wilkoxon test.
RESULTS
In patients with chronic ischemic heart disease with BMI up to 25 we have found
statistically significant increase of maximal symptom-limited performance (Wmax),
statistically significant increase of maximal heart rate (HRmax), maximal oxygen
consumption (VO2max), MET, questionnaire of quality of life with regard to usage of
nitroglycerin at anginous pain (SAQ 3), as it is given in Tables 4, 5, 6.
143
Table 4. Results of symptom-limited spiroergometry before exercise therapy in
individual groups of patients with chronic ischemic heart disease divided according
BMI
BMI to 25
(1st
group)
BMI 25,1 – 30
(2nd
group)
BMI over 30
(3rd
group)
Statistical
significance
HR maximal 121.0±13.6 113.5±16.8 109.1±19.1 NS
W maximal (W) 114.7±34.9 109.5±29.6 121.4±39.3 NS
SBPmax mmHg 204.7±35.5 193.7±25.2 198.8±29.2 NS
DBPmax mmHg 101.7±10.3 106.2±13.2 121.4±39.3 NS
VO2max (ml/min) 1649±389 1643±373 1833±493 NS
VO2 max/kg 22.4±5.3 19.5±4.4 19.1±4.9 *
SAQ 1 85.8±16.8 78.1±20.2 78.6±15.7 NS
SAQ 2 77.1±19.0 77.5±22.1 83.0±22.7 NS
SAQ 3 83.3±17.2 82.8±16.0 84.5±16.3 NS
SAQ 4 91.6±17.1 85.9±17.4 90.5±11.3 NS
SAQ 5 70.0±19.6 63.7±17.8 71.1±14.5 NS
In the column statistical significance *, +, o - p< 0.05, **, ++, oo - p< 0.01;
BMI: up to 25 versus 25.1 -30: *; up to 25 versus over 30: +, 25.1 30 versus over 30: o.
Statistical significance of the difference before rehabilitation and after it is given next to
the relevant value (* p< 0.05, ** p< 0.01)
Table 5 Results of symptom-limited spiroergometry after rehabilitation in individual
groups of patients with chronic ischemic heart disease
BMI to 25
(1st
group)
BMI 25,1 – 30
(2nd
group)
BMI over 30
(3rd
group)
Statistical
significance
HR maximal 133.9±17.6* 114.1±19.5 109.4±21.5 NS
W maximal (W) 133.9±39.0* 118.3±32.8* 126.2±39.0 NS
TKs max mmHg 209.0±30.2 198.2±26.2 211.4±25.2* NS
TKd max mmHg 106.0±15.7 106.0±15.1 126.2±39.0 NS
VO2 max (ml/min) 1964±470** 1756±424 1921±457 **
VO2 max/kg 26.5±6.4* 20.8±5.2* 20±4.4 NS
SAQ 1 88.8±15.3 83.0±16.6* 85.8±14.2** NS
SAQ 2 85.3±16.0 85.0±16.2* 89.0±16.5 NS
SAQ 3 88.3±14.7* 87.7±15.4** 89.2±12.4* NS
SAQ 4 93.3±12.3 92.7±10.9** 93.3±8.1 NS
SAQ 5 72.9±18.0 71.2±18.5** 80.0±14.0** NS
In the column statistical significance *, +, o - p< 0.05, **, ++, oo - p< 0.01;
BMI: up to 25 versus 25.1 -30: *; up to 25 versus over 30: +, 25.1 30 versus over 30: o.
Statistical significance of the difference before rehabilitation and after it is given next to
the relevant value (* p< 0.05, ** p< 0.01)
144
We have achieved considerably different results in the studied groups. It follows
from what was given above, that the patients with a normal body mass attained
significant improvement in maximal achieved physical performance, in maximal
achieved heart rate and maximal oxygen intake. In the patients with overweight we
demonstrated significant increase of maximal achieved physical performance and
maximal oxygen intake related to kilogram of body mass. In the patients with obesity
we achieved significant decrease of systolic pressure and heart rate at rest.
By evaluation of individual items of the questionnaire SAQ we have found out that
in the group of the patients with BMI up to 25 significant improvement was achieved in
frequency of anginous pain and necessity of taking nitroglycerin. In the overweight
group the patients indicated significant improvement in all items of the questionnaire
SAQ. In the group of obese patients improvement was indicated in the questionnaire
items concerning occurrence of anginous pain (SAQ 1), general perception of quality of
life (SAQ 5) and also SAQ 3.
DISCUSSION
Regular combined exercise training of a suitable intensity results in adaptation of
organism to the load, in increase of physical performance and capacity of the transport
system and in quality of life.
In the presented study we were dealing with the role of obesity in this process of
rehabilitation. Individual groups differed only in the body mass index before the
beginning of rehabilitation process. The exception was maximal transport capacity for
oxygen, that was lower in the group of obese patients; it can be easily explained by a
lower proportion of muscular mass and bigger proportion of adipose tissue mass.
Comparison of individual groups after the completion of exercise therapy brought the
same results. This fact demonstrates that in all body mass groups there are considerable
inter-individual differences. We also did not find out any differences in subjective
evaluation of quality of life before exercise therapy and after its completion.
Comparison of individual objective indicators and of subjective evaluation before
physiotherapy and after it gives a different view. Substantial increase of quality of life
145
along with improvement of maximal physical performance and maximal capacity of
oxygen transport system occurs in the group of patients with overweight. In the patients
with normal body mass and in the patients with obesity we can observe less noticeable,
but statistically significant improvement of subjectively evaluated indicators. Only in
the patients with a normal body mass this subjectively perceived condition is
accompanied by increase of maximal physical performance. This was not found in
obese patients.
Our results show that the body mass influences considerably a subjectively perceived
degree of disablement influenced by training. The reality that in obese patients their
physical performance has not been improved is probably due to the fact that their
overweight represents such a strain on the organism, that probably their ischemic heart
has not enough additional reserves which would appear with increased maximal
physical performance. The conclusions following from our study are not pessimistic in
the case of obese patients, however. Even if their physical performance has not been
improved, improvement of subjectively experienced quality of life turned out, and it is
more important for the therapy. It seems that intensive pressure on decreasing the body
mass could bring about still more favourable results of exercise training for the patient.
CONCLUSION
The paper aims at evaluation of the impact of the twelve-week combined training on
quality of life, physical performance and capacity of the transport system of the patients
depending on their body mass.
On the basis of the input symptom-limited spiroergometry and of the same
examination carried out after the termination of the training we have proved that the
twelve-week combined exercise training in patients with chronic ischemic heart disease
resulted in increasing their physical performance and capacity of the transport system,
particularly in the patients with the body mass index lower than 30. As to the patients
with the body mass index higher than 30, we have not observed any increase of physical
performance. We have found, however, that all groups of patients subjectively
experienced improvement of their quality of life. We have thus shown that even if the
146
rehabilitation training does not lead to improved physical performance, it can bring
about subjectively experienced improvement of quality of life.
Supported by MSM0021622402
REFERENCES
1. CHALOUPKA, V., SIEGELOVÁ, J. ŠPINAROVÁ, L. a kol. 2006. Rehabilitace u
nemocných s kardiovaskulárním onemocněním. Cor Vasa. 48: K 127-45.
2. JANČÍK, J. – DOBŠÁK, P. – SVAČINOVÁ, H. – SIEGELOVÁ, J. – PLACHETA,
Z. 2002. Zátěžová vyšetření u nemocných s chronickým srdečním selháním.
Kardiol. Revue, roč. 3., s. 175-179.
3. JANČÍK, J. – VANK, P. – MÍFKOVÁ, L. – CHLUDILOVÁ, V. – FIŠER, B. –
SIEGELOVÁ, J. – EICHER, J. CH. 2004. Aerobní trénink kombinovaný se
silovými prvky u nemocných s chronickou ischemickou chorobou srdeční: vliv na
variabilitu srdeční frekvence. In Optimální působení tělesné zátěže a výživy. Hradec
Králové: Gaudeamus, s. 213-216, ISBN 80-7041-666-1
4. MARTINÍK, K. 2005. Individuální výběr nemocných pro silový trénink u
nemocných po akutním infarktu myokardu se sníženou ejekční frakcí levé komory –
editioral. Vnitřní lékařství, roč. 51., č. 1., s. 13-16.
5. NIEDERLE, P. 2004. Rehabilitace a trénink u kardiaků. In ASCHERMANN, M. et
al. Kardiologie. Praha: Galén, s. 1421-1424.
6. PLACHETA, Z. – SIEGELOVÁ, J. – ŠTEJFA. et al. 1999. Zátěžová diagnostika
v ambulantní a klinické praxi. Grada Publishing, s. 51-178, ISBN 80-7169-271-9
7. DRAGOMIRECKÁ, E. – ŠKODA, C. 1997. Kvalita života. Vymezení, definice a
historický vývoj pojmu v sociální psychiatrii. Č. S. Psychiatrie, roč. 93, č.2, s. 102-
108.
8. SLOVÁČEK, L. – SLOVÁČKOVÁ, B. – JEBAVÝ, L. – BLAŽEK, M. –
KUČEROVSKÝ, J. 2004. Kvalita života nemocných – jeden z důležitých parametrů
komplexního hodnocení léčby. Vojenské zdravotnické listy, roč. 73, č.1, s. 6-9.
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9. SLOVÁČEK, L. Kvalita života a ischemická choroba dolních končetin. Interv Akut
Kardiol 2006;5:207–210
10. PAYNE, J. A KOL. 2002. Zdraví: hodnota a cíl moderní medicíny. Praha: Triton, s.
9-12, s. 54-64, ISBN 80-7254-293-1
SUMMARY
The paper deals with evaluation of the impact of the 12-week combined exercise
training on quality of life, physical performance and capacity of the transport system of
patients with chronic ischemic heart disease (n = 88) depending on the body mass of the
patients.
On the basis of the input spiroergometric examination and of the same examination
carried out after the termination of the training we have proved that the 12-week
combined exercise training in patients with chronic ischemic heart disease resulted in
increasing their physical performance and capacity of the transport system, particularly
in the patients with the body mass index lower than 30. As to the patients with the body
mass index higher than 30, we have not observed any increase of physical performance.
We have found, however, that all groups of patients subjectively experienced
improvement of their quality of life. We have thus shown that even if the rehabilitation
training does not lead to improved physical performance, it can bring about subjectively
experienced improvement of quality of life.
KEY WORDS
Quality of life, combined training, cardiovascular rehabilitation, chronic ischemic
heart disease, obesity
148
EXERCISE TRAINING IN MEN AFTER CORONARY ARTERY
BYPASS SURGERY
Veronika Chludilová, Leona Mífková, Jaroslava Pochmonová, František Várnay,
Michal Pohanka, Nabil Abdulah Ibrahim Al-Mahmodi, Mohsin Kaid Ali Hashim,
Jaroslava Pochmonová, Abdul Karim Al Fadhli, Farag Hassan Anbais, Ashref Ali Erajhi,
Alena Havelková, Jarmila Siegelová
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine,
Masaryk University, St. Anna Teaching Hospital, Brno, CZ
INTRODUCTION
Cardiovascular rehabilitation is a universally accepted part of the complex care of patients
with cardiovascular disease (1). It increases physical fitness, improves quality of life (2-4) and
decreases cardiovascular mortality (5,6). Dynamical endurance aerobic activities (walking,
cycling, jogging, swimming, etc.) are the basis of cardiovascular rehabilitation programs (7-
9). As a certain level of muscular strength that can be diminished in patients with ischemic
heart disease (9,10) is necessary for a number of working and recreational activities,
usefulness of resistance training as an adjuvant component of rehabilitation programs for
cardiac patients has been considered (9). In spite of a concern as to cardiovascular safety of
resistance training, resistance exercises proved to be a safe part of cardiovascular
rehabilitation (1, 9-16).
PURPOSE OF THE STUDY
The purpose of the study was to examine the effect of 12-week controlled out-patient
rehabilitation program on muscle strength and selected indicators of physical fitness and
performance and to verify safety and effectiveness of combination of aerobic and resistance
training in patients after coronary artery bypass surgery (ACB).
149
SET OF PATIENTS
10 men after ACB aged 64 ± 7 years, with mean ejection fraction of left ventricle 49 ± 11 %,
who were at least 6 weeks (40 ± 28 weeks) after the surgery, were included into the study.
All subjects gave their informed approval.
METHODOLOGY
Methods of examination
Before the beginning of exercise training (RHB) program and after its completion we
made symptom-limited spiroergometry to symptom-limited maximum (Pulmonary Function
System 1070, MedGraphics, USA). The examination was started by monitoring resting ECG
in lying and sitting position (Schiller CS 100), followed by 3-minute adaptation in sitting
position on ergometer. Load was increased every 2 minutes by 20 W to symptom-limited
maximum. Anaerobic threshold was determined from the course of changes of ventilationrespiration
parameters. The values of load, heart rate and RPE for the training were
determined at the anaerobic threshold level.
Before the beginning of resistance training (i.e. in the 3rd
week of RHB program) we made
isometric test („handgrip“, DHG-SY3, Recens) to verify blood pressure response to isometric
load. In the case of a normal response the entrance 1-RM test (one repetition maximum test)
was made in three exercises of resistance training. The test was repeated in the 6th
week and in
the 12th
week of RHB program.
Rehabilitation program
The outpatient controlled RHB program lasted 12 weeks altogether with frequency three
times a week. The training unit lasted 60 minutes and consisted of several phases (table 1).
150
Table 1. Composition of the training unit
1st
– 2nd
week only aerobic training 3rd
– 12th
week combined training
10 min warm-up phase 10 min warm-up phase
40 min aerobic phase 25 min aerobic phase
10 min relaxation phase 15 min resistance training
10 min relaxation phase
Warm-up phase was aimed at preparing cardiovascular and motor system to further load,
prevention of muscular-skeletal lesion. It consisted of dynamical endurance exercises (simple
floor gymnastic exercises, exercises gymnastic apparatus) and stretching of muscle groups
with a tendency to shortening.
Aerobic phase was effected on a bicycle ergometer (Ergoline REHA E900) controlled by
the program ErgoSoft+ for Windows. The aerobic training intensity was determined at the
anaerobic threshold level.
Resistance training was realized on multifunctional muscle conditioning machines TK-HC
COMPACT. 4 exercises were done (bench press, pull down, leg extension on the machine and
sitting-lying positions). Resistance training intensity was determined by the method 1-RM and
training loads were determined in percents of maximum: 30-60 % 1-RM (each week increase
by 10 %). The number of sequences was 3 - 5 with the number of repetitions 10x. Before
starting the resistance training, the patients were thoroughly informed about proper breathing
and technique of doing exercises.
Modified Schultz autogenic training was used for relaxation.
In the course of the whole training monitoring of heart rate, blood pressure and degree of
RPE, during the aerobic phase and in 1-RM test also ECG was carried out.
RESULTS
The effect of 12-week controlled out-patient rehabilitation program showed in patients
after coronary artery bypass surgery a statistically significant increase of symptom-limited
oxygen intake and oxygen intake converted to kg of body mass (evaluated also at anaerobic
threshold level Table 2) was recorded.
151
Table 2. Parameters of aerobic capacity in patients after coronary artery bypass surgery
before and after 12-week controlled out-patient rehabilitation program
Before RHB After RHB p
VO2SL (ml.min-1
) 1452 ± 292.2 1789± 459.6 >0.05
VO2SL/kg (ml.min-1
.kg-1
) 16.5 ± 3.32 20.3 ± 5.94 >0.05
VO2ANP (ml.min-1
) 1003 ± 191.5 1151 ± 220.1 >0.01
VO2SL = symptom-limited oxygen intake, VO2ANP = oxygen intake at anaerobic threshold level
Symptom-limited performance and performance converted to kg of body mass (evaluated also
at anaerobic threshold level Table 3) were also increased.
Table 3. Performance parameters in patients after coronary artery bypass surgery before
and after 12-week controlled out-patient rehabilitation program
Before RHB After RHB p
WSL (W) 89 ± 16.6 123 ± 36.2 >0.05
WSL/kg (W.kg-1
) 1.0 ± 0.25 1.4 ± 0.49 >0.05
WANP (W) 46 ± 13.5 66 ± 18.6 >0.05
WSL = symptom-limited performance, WANP = performance at anaerobic threshold level
Muscle strength of the groups being trained was also considerably increased (table 4).
Table 4. Performance in 1-RM test in patients after coronary artery bypass surgery before
and after 12-week controlled out-patient rehabilitation program
Before RHB After RHB p
Bench press (kg) 31 ± 9.4 38 ± 6.9 >0.01
Pull down (kg) 29 ± 8.7 35 ± 7.5 >0.01
Leg extension (kg) 30 ± 9.3 36 ± 8.7 >0.01
Statistical processing was made in the programs Microsoft Excel and Statistica, version 7.
Distribution was tested by Lillefors modification of Kolmogorov-Smirnov test of normality.
Some parameters had normal distribution Wilcoxon test was used for all parameters.
Our results in patients after coronary artery bypass surgery showed statistically significant
increase of capacity of the transport system (1441 ± 307.7 vs. 1768 ± 482.2 ml.min-
1),
physical performance (90 ± 17.3 vs. 120 ± 37.4 W) and muscular strength (bench press 30 ±
9.8 vs. 36 ± 9.1 kg, pull down 30 ± 9.4 vs. 37 ± 6.6 kg, leg extension 30 ± 8.6 vs. 36 ± 7.8 kg)
was recorded.
152
DISCUSSION
After thoracotomy the capacity for physical performance of the patients is limited. Healing
of the lesion takes 4 – 6 weeks on average. The first 3 months after the surgery physical strain
causing tangential acting of forces and pressure on the sternum region should be
contraindicated. Before starting the resistance training the attending physician must confirm
that sternum is stable (4, 17-19). If there are no postoperative complications and the patient is
compensated from cardiologic point of view, effortless muscle conditioning exercises directed
at lower extremities can be started even sooner (20).
From the study of Maiorany et al. it follows that mere resistance training does not lead to
the increase of symptom-limited oxygen intake. The authors monitored in their study, apart
from other things, influence of 10-week resistance training on muscle strength in 26 men after
ACB. The training unit included warm-up phase and stretching (5 min), resistance training
(36 min) and relaxation phase (5 min). The patients did 12 exercises altogether (7 for upper
extremities, 4 for lower extremities and 1 exercise for strengthening of abdominal muscles).
At the beginning of the training the patients completed 1 cycle (so called „round“) of
exercises with intensity 40 % of maximal voluntary contraction (MVC) with the ratio of effort
and rest 1:1 (30 s effort and 30 s rest). The number of repetitions was 10 - 15. Intensity in the
first 2 weeks was increasing in such a way that the number of cycles increased to 2 – 3,
according to capabilities of the patient. From the 2nd
week all patients were already doing
exercises with 40 % of MVC in 3 cycles, by the 4th
week intensity was increased to 50 % of
MVC, from the 6th
week the ratio of effort and rest was changed to 2:1 (40 s effort and
20 s rest), from the 8th
week intensity was increased to 60 % of MVC. This study confirmed
that resistance training of a low to medium intensity in suitably chosen patients is safe and
represents an effective stimulus for the increase of muscle strength of big muscular groups in
men after ACB (21).
After the group of men went through the 12-week training with combined load, we also
observed a considerable increase of muscle strength of the trained muscular groups. Due to
combination of resistance and aerobic training also aerobic capacity and load tolerance were
substantially increased.
Combination of aerobic and resistance training with intensity at anaerobic threshold level
seemed in practise to be safe and adequately physiologically effective on condition of a
correct choice of patients and their careful continuous checking.
153
Provided that safe limits are complied with, combined training associates positive effects
of aerobic and resistance exercise and seems to be optimal for the group of patients we have
been monitoring. A favourable effect of the training continues only if the patient pursues
regular exercising. If no regular physical exercise follows after the rehabilitation program, the
values of aerobic capacity and physical performance return to the level before the training
approximately within the time as long as was the time of duration of the regular training.
CONCLUSION
12-week combined training in men after coronary artery bypass surgery resulted in increasing
oxygen capacity transport by 23 %, physical performance by 38 % and muscle strength by
20 %.
Supported by MSM0021622402.
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17. Sparing PB, et al. Strength training in a cardiac rehabilitation program: a six month
follow up. Arch Phys Med Rehabil.1990;71:148-152.
18. McCartney N, et al. The role of resistance training in patients with cardiac disease.
J Cardiovasc Risk.1996;3:160-166.
19. Fletcher GF, et al. Exercise standards for testing and training. A statement for
healthcare professionals from the American Heart Association. Circulation.
2001;104:1694-1740.
20. Bjarnason-Wehrens B, et al. Recommendations for resistance exercise in cardiac
rehabilitation. Recommendations of the German federation for cardiovascular
prevention and rehabilitation. Euro J Cardiovasc Prev Rehabil.2004; 11(4):352-361.
21. Maiorana AJ, et al. A controlled trial of circuit weight training on aerobic capacity and
myocardial oxygen demand in men after coronary artery bypass surgery. J
Cardiopulm Rehabil. 1997;17:239-247.
155
SUMMARY
The purpose of the study was to examine the effect of 12-week controlled out-patient
rehabilitation program with combined load on muscle strength and selected indicators of
physical fitness and performance and to verify safety of the program in men after coronary
artery bypass grafting (CABG). Nine men after CABG aged 64 ± 7 years, with mean ejection
fraction of left ventricle 50 ± 12 % were included. Before the rehabilitation program and after
it symptom-limited spiroergometry was made up to symptom-limited maximum. The training
intensity was determined at the level of anaerobic threshold. Isometric test (“handgrip”) was
made before the beginning of resistance training. If the response was normal, 1-RM test (one
repetition maximum test) was made. Statistically significant increase of capacity of the
transport system (1441 ± 307.7 vs. 1768 ± 482.2 ml.min-
1),physical performance (90 ± 17.3
vs. 120 ± 37.4 W)and muscular strength (bench press 30 ± 9.8 vs. 36 ± 9.1 kg, pull down 30 ±
9.4 vs. 37 ± 6.6 kg, leg extension 30 ± 8.6 vs. 36 ± 7.8 kg) was recorded.
KEY WORDS
Cardiac exercise therapy, aerobic training, resistance training, coronary artery bypass surgery
156
FUNCTIONAL EVALUATION IN CHILDREN WITH CEREBRAL PALSY AFTER
6-MONTH THERAPY
Lenka Drlíková1
, Mohsin Kaid Ali Hashim2
,
Abdul Karim Al Fadhli2
, Farag Hassan Anbais2
, Ashref Ali Erajhi2
, Petr Pospíšil2
,
Lumír Konečný2
, Helena Zemanová1
, Jarmila Siegelová2
1
The Home for Handicapped Children and Young Adults Kociánka,
Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk
University, St. Anna Teaching Hospital, Brno, CZ
INTRODUCTION
Cerebral palsy is a syndrome characterized by disorder of postural tonus, coordination
of movements and senses. It is therefore a sensory motor disease originating on the basis of
non-progressive immature brain damage. (1). The syndrome has been existing for many years
already in both more and less advanced communities with a relatively constant incidence of 2-
5 per mil. The reason of fluctuation in this range has not been reliably demonstrated yet. (2)
With regard to the fact that this disease does not reduce substantially the life-span, cerebral
palsy is an important social problem. It requires lifelong assistance that is often necessary,
costs of repeated orthopaedic operations and compensatory aids, rehabilitation treatment,
brings about problems with professional engaging, and last but not least, affects quality of life
of the patients. (2,3)
There are many studies monitoring the changes connected with different kinds of both
intervening and non intervening therapies. The most frequently evaluated criteria include
changes in the base (4,5), range of movements (4), changes in balance (6). The studies
monitoring different approaches in the therapy of these patients have controversial results.
(7,8,9)
157
AIM
The aim of the study is to compare possibilities of evaluation of changes of the
functional state of children with cerebral palsy by means of the tests: “Gross Motor Function
Measure” (GMFM) (10) and 100-point test “Barthel Index” (ADL) evaluating 10 the most
important self attendance activities (11, 12). We monitor the functional state change after 6
months and we evaluate the changes for individual groups of patients. The results of the study
are preliminary ones.
METHODS
We examined 15children with cerebral palsy at the age 5- 16 years, average age was
11.94 ± 4.12 years. Individual CP forms percentages were as follows: spastic 93 %, nonspastic
7 %, diplegia 47 %, hemiplegia 13 %, quadruplegia 33 %, ataxia 7 %. We used the test
Gross Motor Function Measure - GMFM and the test of daily activities Barthel index.
The children were treated by methods of comprehensive rehabilitation using Bobath
concept (33.3 %), in some cases exercises on analytic basis (66.6 %) prescribed by their
doctor were used.
After 6 months of the prescribed therapy the same examination was repeated.
GMFM test includes evaluation of 88 items divided into 5 sections – 1. lying and
rolling, 2. sitting, 3. crawling and kneeling, 4. standing, 5. walking, running and jumping. It
evaluates skills of the child in individual items by using a 4-point scale on the quantitative
basis. A healthy child at the age of five years should comply with all items. The protocol of
the study was approved by the local ethical commission.
Barthel index ADL test evaluates 10 most important self attendance activities. It is
used for assessment of the patient's independence. The need of supervising means a certain
degree of dependence. We record what the patient is really doing, not what is his potential.
We expressed the results as average values (± SD). We evaluated also correlation
between the first and the second examinations. We used a Wilcoxon test for paired values for
the evaluation of our results.
158
RESULTS
In the first evaluation by GMFM in children with cerebral palsy as a whole reached
the total score from 21 to 97 %, in the second evaluation after 6 months the group in GMFM
test reached the score in the range 25- 99 %. The results of the test GMFM1 (before the
treatment) showed 58.8±23.1 points and after 6 months GMFM2 showed 63.6±22.8 points,
which is statistically significant improvement (p < 0.01).
In ADL test the same group of children with cerebral palsy reached the total score 20-
100 %, on average 60±32 %. In ADL test made after six months the total score was 25-100 %,
on average 64±31 %; the second measurement was statistically significant (p<0.05). We
evaluated several parts of GMFM test, individual items of GMFM tests are in Table 1.
Table 1. GMFM test of children with cerebral palsy in first examination and examination after
6 months in individual items A to E of GMFM (A = lying and rolling, B = sitting, C =
crawling and kneeling, D = stand, E = walking, running and jumping)
n = 15 A B C D E
1st
examination 63.6±22.8 91.9±8.3 77±25.6 44±40.3 56.8±34.2
2nd
examination 58.8±23.1 93.4±6 78.9±26.2 41.4±39.2 59.4±34.1
The differences in individual items are not statistically significant.
We have not proved an improvement after 6 months in individual items of GMFM test.
Our results showed after the therapy lasting half a year in children with cerebral palsy a
statistically significant improvement both in GMFM test and ADL test. Individual items of
GMFM were not substantially changed.
159
Graph No. 1 Correlation between first and second examination using „Gross Motor Function
Measure“ (GMFM) in the measurement made before and after six months PT treatment
DISCUSSION
Our results in children with cerebral palsy of the scores achieved in individual tests
being presented are in accordance with the results of our sample of 30 CP children already
published (13), and also with other studies dealing with these problems (10, 11, 12). The test
GMFM, compared to Barthel index, proves to be an identically sensitive test evaluating the
results after 6-month rehabilitation.
Our study is limited by the fact that the syndrome is non-homogenous, and if we want
to form homogenous groups, we are limited by an insufficient number of subjects. Obtaining
more valid data means extension of the study to a longer period, which will also enable
statistical evaluation of various forms of the disease and different therapeutic methods.
Korelace GMFM1 a GMFM2
0
20
40
60
80
100
120
0 20 40 60 80 100 120
GMFM1
GMFM2
160
CONCLUSION
After the therapy of children with cerebral palsy, lasting half a year a statistically
significant improvement both in GMFM test and ADL test was achieved. Individual items of
GMFM were not substantially changed.
Supported by MSM0021622402
LITERATURE
1. Chmelová I. DMO. Zpráva ze semináře. Available from:
http://www.mnof.web4u.cz/drs/s20030318/dmo.php
2. Kraus J. a kol. Dětská mozková obrna. Grada. Praha, 2005. ISBN 80-247-1018-8
3. Jankovský J. Ucelená rehabilitace dětí s tělesným a kombinovaným postižením. Triton.
Praha, 2006. ISBN: 80-7254-730-5
4. Galarza M., Fowler E.G., Chipps L., Padden T.M., Lazareff J.A. Functional Assessment of
Children with Cerebral Palsy Following Limited (L4-S1) Selective Posterior Rhizotomy - A
Preliminary Report. Acta neurochirurgica 2001; 143 (9): 865- 872.
5. Lucareli P.R.G., Lima M.O., Lucarelli J.G.A., Lima F.P.S. Changes in joint kinematics in
children with cerebral palsy while walking with and without a floor reaction ankle-foot
orthosis . Clinics 62, 1. Available from:
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-
59322007000100010&lng=eneng&nrm=iso&tlng=eneng
6. Rose J, Wolff DR, Jones VK, Bloch DA, Oehlert JW, Gamble JG. Postural balance in
children with cerebral palsy. Dev Med Child Neurol 2002; 44 (1): 58-63.
7. Krigger K. Cerebral Palsy: An Overview. Am Fam Physician 2006; 73: 91-102.
161
8. Sankar C.,Mundkur N., Cerebral palsy - definition, classification, etiology and early
diagnosis. Indian J Pediatr [serial online] 2005; 72: 865-868. Available from:
http://www.ijpediatricsindia.org/article.asp?issn=0019-
5456;year=2005;volume=72;issue=10;spage=865;epage=868;aulast=Sankar
9. Tsorlakis N., Evaggelinou C., Grouios G., Tsorbatzoudis C. Effect of intensive
neurodevelopmental treatment in gross motor function of children with cerebral palsy. Dev
Med Child Neurol 2005; 47 (4):287-289
10. Russel D., Rosenbaum P., Gowland C., Hardy S., Lane M., Plews N., Hc Gawin H.,
Cadman D., Jarvis S. Gross Motor Function Measure Manual. Hamilton: Mc Master
University. Second edition 1993, 112.
11. Mahoney FI, Barthel D. Functional evaluation: the Barthel Index. Maryland State Med
Journal 1965;14:56-61.
12. Masur H. Scales and Scores in Neurology. Quantification of Neurological deficits in
Research and Practice. New York: Thieme 2004; s. 392-393.
13. Drlíková L., Pospíšil P., Konečný L., Chludilová V., Siegelova J., Fišer B., Pochmonova
J., Erajhi A.A., Abais F.H., Hashim M.K.A., Al-Fadhli A., Al- Mahmodi N.A.I., Vank P.
Functional Impairment in children with cerebral palsy In: Noninvasive methods in cardiology.
NCONZO, Brno 2006.
Summary
Introduction: Cerebral palsy is a syndrome connected with immature brain damage. This
disease means a serious social and economic problem. There are lots of studies concerned
with treatment of cerebral palsied individuals, but their results are dissimilar.
Aims: The aim of this study is to compare functional changes using two different methods Gross
Motor Function Measure (GMFM) and Barthel Index (BI). GMFM consists of 88 tasks
divided into 5 sections. BI evaluates everyday activities of the patient.
162
Results: We examined 15 children 5-16 years old (average age was 11.94±4.12 years). The
percentages of groups of different CP forms were as follows: spastic 93 %, non-spastic 7 %;
diplegia 47 %, hemiplegia 13 %, quadruplegia 33 %, ataxia 7 %. The children were treated
according to principles of comprehensive rehabilitation treatment (5 of them using Bobath
concept, 10 of them with analytic approach). The group was tested before the treatment and
after 6 months of the treatment. The correlation between both measurements was high.
Our results showed improvements in both tests, GMFM and ADL, after 6 months
lasting rehabilitation treatment.
Key words: cerebral palsy, rehabilitation, functional evaluation, Gross Motor Function
Measure, Barthel index
NÁZEV:	 NONINVASIVE METHODS IN CARDIOLOGY
EDITOR:	 F. HALBERG, T. KENNER, B. FIŠER, J. SIEGELOVÁ
VYDAL	
A VYTISKL:	 NÁRODNÍ CENTRUM OŠETŘOVATELSTVÍ A NELÉKAŘSKÝCH
	 ZDRAVOTNICKÝCH OBORŮ V BRNĚ
	 VE SPOLUPRÁCI S MASARYKOVOU UNIVERZITOU BRNO
VYDÁNÍ:	 PRVNÍ
POČET STRAN:	 162
VYŠLO:	 BRNO 2007
VÝR. ČÍSLO:	 82/2007
TIRÁŽNÍ ZNAK:	 57-864-07