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@article{1674577,
author = {Sutanto, Henry and Cluitmans, Matthijs J.M. and Dobrev, Dobromir and Volders, Paul G.A. and Bébarová, Markéta and Heijman, Jordi},
article_location = {Oxford},
article_number = {September 2020},
doi = {http://dx.doi.org/10.1016/j.yjmcc.2020.07.007},
keywords = {ethanol; cardiac electrophysiology; arrhythmia; computational modeling; atrial fibrillation},
language = {eng},
issn = {0022-2828},
journal = {Journal of Molecular and Cellular Cardiology},
title = {Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses},
url = {https://www.sciencedirect.com/science/article/pii/S0022282820302297},
volume = {146},
year = {2020}
}
TY - JOUR
ID - 1674577
AU - Sutanto, Henry - Cluitmans, Matthijs J.M. - Dobrev, Dobromir - Volders, Paul G.A. - Bébarová, Markéta - Heijman, Jordi
PY - 2020
TI - Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses
JF - Journal of Molecular and Cellular Cardiology
VL - 146
IS - September 2020
SP - 69-83
EP - 69-83
PB - Elsevier
SN - 00222828
KW - ethanol
KW - cardiac electrophysiology
KW - arrhythmia
KW - computational modeling
KW - atrial fibrillation
UR - https://www.sciencedirect.com/science/article/pii/S0022282820302297
L2 - https://www.sciencedirect.com/science/article/pii/S0022282820302297
N2 - 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.
ER -
SUTANTO, Henry, Matthijs J.M. CLUITMANS, Dobromir DOBREV, Paul G.A. VOLDERS, Markéta BÉBAROVÁ and Jordi HEIJMAN. Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses. \textit{Journal of Molecular and Cellular Cardiology}. Oxford: Elsevier, 2020, vol.~146, September 2020, p.~69-83. ISSN~0022-2828. Available from: https://dx.doi.org/10.1016/j.yjmcc.2020.07.007.
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