Possible proarrhythmic stimuli in Y4734C-RYR2 variant
associated with idiopathic ventricular fibrillation

a 2023

Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation

BÉBAROVÁ, Markéta, Olga ŠVECOVÁ, Martin KRÁL, Štefan ZELENÁK, Jiří PACHERNÍK et. al.

Základní údaje

Originální název

Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation

Autoři

BÉBAROVÁ, Markéta (203 Česká republika, garant, domácí), Olga ŠVECOVÁ (203 Česká republika, domácí), Martin KRÁL (203 Česká republika, domácí), Štefan ZELENÁK (703 Slovensko, domácí), Jiří PACHERNÍK (203 Česká republika), Tomáš BÁRTA (203 Česká republika, domácí), Samuel LIETAVA (703 Slovensko, domácí), Iva SYNKOVÁ (203 Česká republika), Jana ZÍDKOVÁ (203 Česká republika, domácí) a Tomáš NOVOTNÝ (203 Česká republika)

Vydání

47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Dánsko

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14110/23:00134665

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

proarrhythmic stimuli; Y4734C-RYR2; idiopathic ventricular fibrillation

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 4. 2024 13:41, Mgr. Tereza Miškechová

Anotace

V originále

Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P  0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), β-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P  0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P  0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, β-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM.

Návaznosti

MUNI/A/1343/2022, interní kód MU

Název: Zátěže kardiovaskulárního systému od A po Z

Investor: Masarykova univerzita, Zátěže kardiovaskulárního systému od A po Z

NU22-02-00348, projekt VaV

Název: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministerstvo zdravotnictví ČR, Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus, Podprogram 1 - standardní

Citovat

BÉBAROVÁ, Markéta, Olga ŠVECOVÁ, Martin KRÁL, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ a Tomáš NOVOTNÝ. Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation. In 47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology. 2023.

@proceedings{2334064,
   author = {Bébarová, Markéta and Švecová, Olga and Král, Martin and Zelenák, Štefan and Pacherník, Jiří and Bárta, Tomáš and Lietava, Samuel and Synková, Iva and Zídková, Jana and Novotný, Tomáš},
   booktitle = {47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
   keywords = {proarrhythmic stimuli; Y4734C-RYR2; idiopathic ventricular fibrillation},
   language = {eng},
   title = {Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation},
   year = {2023}
}

TY  - CONF
ID  - 2334064
AU  - Bébarová, Markéta - Švecová, Olga - Král, Martin - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Lietava, Samuel - Synková, Iva - Zídková, Jana - Novotný, Tomáš
PY  - 2023
TI  - Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation
KW  - proarrhythmic stimuli
KW  - Y4734C-RYR2
KW  - idiopathic ventricular fibrillation
N2  - Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P  0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), β-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P  0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P  0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, β-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM.
ER  -

BÉBAROVÁ, Markéta, Olga ŠVECOVÁ, Martin KRÁL, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ a Tomáš NOVOTNÝ. Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation. In \textit{47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2023.

Podrobný výpis o publikaci