AuthorsK. H. Jæger, A. G. Edwards, W. R. Giles and A. Tveito
TitleArrhythmogenic influence of mutations in a myocyte‑based computational model of the pulmonary vein sleeve
AfilliationScientific Computing
Project(s)Department of Computational Physiology
Publication TypeJournal Article
Year of Publication2022
JournalNature Scientific Reports
PublisherSpringer Nature

In the heart, electrophysiological dysregulation arises from defects at many biological levels (from point mutations in ion channel proteins to gross structural abnormalities). These defects disrupt the normal pattern of electrical activation, producing ectopic activity and reentrant arrhythmia. To interrogate mechanisms that link these primary biological defects to macroscopic electrophysiologic dysregulation most prior computational studies have utilized either (i) detailed models of myocyte ion channel dynamics at limited spatial scales, or (ii) homogenized models of action potential conduction that reproduce arrhythmic activity at tissue and organ levels. Here we apply our recent model (EMI), which integrates electrical activation and propagation across these scales, to study human atrial arrhythmias originating in the pulmonary vein (PV) sleeves. These small structures initiate most supraventricular arrhythmias and include pronounced myocyte‑to‑myocyte heterogeneities in ion channel expression and intercellular coupling. To test EMI’s cell‑based architecture in this physiological context we asked whether ion channel mutations known to underlie atrial fibrillation are capable of initiating arrhythmogenic behavior via increased excitability or reentry in a schematic PV sleeve geometry. Our results illustrate that EMI’s improved spatial resolution can directly interrogate how electrophysiological changes at the individual myocyte level manifest in tissue and as arrhythmia in the PV sleeve.

Citation Key42456