J 2020

Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses

SUTANTO, Henry, Matthijs J.M. CLUITMANS, Dobromir DOBREV, Paul G.A. VOLDERS, Markéta BÉBAROVÁ et. al.

Základní údaje

Originální název

Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses

Autoři

SUTANTO, Henry (528 Nizozemské království), Matthijs J.M. CLUITMANS (528 Nizozemské království), Dobromir DOBREV (276 Německo), Paul G.A. VOLDERS (528 Nizozemské království), Markéta BÉBAROVÁ (203 Česká republika, domácí) a Jordi HEIJMAN (528 Nizozemské království, garant)

Vydání

Journal of Molecular and Cellular Cardiology, Oxford, Elsevier, 2020, 0022-2828

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 5.000

Kód RIV

RIV/00216224:14110/20:00116225

Organizační jednotka

Lékařská fakulta

DOI

UT WoS

000571869800001

Klíčová slova anglicky

ethanol; cardiac electrophysiology; arrhythmia; computational modeling; atrial fibrillation

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 8. 10. 2020 08:21, Mgr. Tereza Miškechová

Anotace

V originále

Acute excessive ethyl alcohol (ethanol) consumption alters cardiac electrophysiology and can evoke cardiac arrhythmias, e.g., in ‘holiday heart syndrome’. Ethanol acutely modulates numerous targets in cardiomyocytes, including ion channels, calcium-handling proteins and gap junctions. However, the mechanisms underlying ethanol-induced arrhythmogenesis remain incompletely understood and difficult to study experimentally due to the multiple electrophysiological targets involved and their potential interactions with preexisting electrophysiological or structural substrates. Here, we employed cellular- and tissue-level in-silico analyses to characterize the acute effects of ethanol on cardiac electrophysiology and arrhythmogenesis. Acute electrophysiological effects of ethanol were incorporated into human atrial and ventricular cardiomyocyte computer models: reduced INa, ICa,L, Ito, IKr and IKur, dual effects on IK1 and IK,ACh (inhibition at low and augmentation at high concentrations), and increased INCX and SR Ca2+ leak. Multiscale simulations in the absence or presence of preexistent atrial fibrillation or heart-failure-related remodeling demonstrated that low ethanol concentrations prolonged atrial action-potential duration (APD) without effects on ventricular APD. Conversely, high ethanol concentrations abbreviated atrial APD and prolonged ventricular APD. High ethanol concentrations promoted reentry in tissue simulations, but the extent of reentry promotion was dependent on the presence of altered intercellular coupling, and the degree, type, and pattern of fibrosis. Taken together, these data provide novel mechanistic insight into the potential proarrhythmic interactions between a preexisting substrate and acute changes in cardiac electrophysiology. In particular, acute ethanol exposure has concentration-dependent electrophysiological effects that differ between atria and ventricles, and between healthy and diseased hearts. Low concentrations of ethanol can have anti-fibrillatory effects in atria, whereas high concentrations promote the inducibility and maintenance of reentrant atrial and ventricular arrhythmias, supporting a role for limiting alcohol intake as part of cardiac arrhythmia management.

Návaznosti

MUNI/A/1307/2019, interní kód MU
Název: Kardiovaskulární systém od A do Z (Akronym: KAVASAZ)
Investor: Masarykova univerzita, Kardiovaskulární systém od A do Z, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty