Detailed Information on Publication Record
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.Basic information
Original name
Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses
Authors
SUTANTO, Henry (528 Netherlands), Matthijs J.M. CLUITMANS (528 Netherlands), Dobromir DOBREV (276 Germany), Paul G.A. VOLDERS (528 Netherlands), Markéta BÉBAROVÁ (203 Czech Republic, belonging to the institution) and Jordi HEIJMAN (528 Netherlands, guarantor)
Edition
Journal of Molecular and Cellular Cardiology, Oxford, Elsevier, 2020, 0022-2828
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30105 Physiology
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 5.000
RIV identification code
RIV/00216224:14110/20:00116225
Organization unit
Faculty of Medicine
UT WoS
000571869800001
Keywords in English
ethanol; cardiac electrophysiology; arrhythmia; computational modeling; atrial fibrillation
Tags
International impact, Reviewed
Změněno: 8/10/2020 08:21, Mgr. Tereza Miškechová
Abstract
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.
Links
| MUNI/A/1307/2019, interní kód MU |
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