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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00116225" target="_blank" >RIV/00216224:14110/20:00116225 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0022282820302297" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0022282820302297</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.yjmcc.2020.07.007" target="_blank" >10.1016/j.yjmcc.2020.07.007</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular and Cellular Cardiology

ISSN

0022-2828

e-ISSN

1095-8584

Volume of the periodical

146

Issue of the periodical within the volume

September 2020

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

69-83

UT code for WoS article

000571869800001

EID of the result in the Scopus database

2-s2.0-85088790918