Combination of Pharmacokinetic and Electrophysiology Modeling for Simulating Alcohol-Induced Arrhythmias

Vladimir Sobota1, Martin Kral2, Jason Bayer3, Jordi Heijman4, Marketa Bebarova5
1Masaryk University, 2Masaryk University (Department of Physiology, Faculty of Medicine), Brno, Czechia, 3IHU LIRYC - University of Bordeaux, 4Dept of Cardiology, Maastricht University, 5Masaryk University, Faculty of Medicine, Department of Physiology


Abstract

Introduction: Alcohol consumption is associated with an increased risk of atrial fibrillation. The extent to which different ethanol pharmacokinetics in men and women contribute to this risk remains unclear. This study investigates the acute effects of commonly observed blood alcohol concentrations (BACs) on atrial arrhythmia vulnerability, with a particular focus on sex-specific ethanol pharmacokinetics.

Methods: A 3-compartment model of ethanol pharmacokinetics with specific parametrization for a male and female subject was used. Peak BACs were obtained for ethanol doses of 10-50g, corresponding to 1-5 standard drinks, respectively. A patient-derived model of the human atria was used and the ethanol effect on ionic currents was modeled. Re-entry was induced by rapid pacing at 12 anatomically-defined sites, considered inducible if persisted for >1s and monitored for 10s.

Results: Re-entrant arrhythmia was inducible in all chronic AF simulations. The presence of either male- or female-specific BACs resulted only in small differences in arrhythmia inducibility (58.3 [56.3, 68.8]% vs. 58.3 [52.1, 66.7]%, p=0.75) and total arrhythmia duration (52.2 [51.0, 74.6]s vs. 55.2 [27.8, 64.0]s, p=0.44).

Conclusion: The results indicate that sex-specific differences in ethanol pharmacokinetics play only a minor role in acute alcohol-induced atrial arrhythmias.