title: The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks.
abstract: Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.
authors.affiliation: Computing Laboratory, University of Oxford, Oxford, OX1 3PG, UK. Thushka.Maharaj@comlab.ox.ac.uk
authors.forename: Thushka
authors.initials: T
authors.lastname: Maharaj
authors.forename: Robert
authors.initials: R
authors.lastname: Blake
authors.forename: Natalia
authors.initials: N
authors.lastname: Trayanova
authors.forename: David
authors.initials: D
authors.lastname: Gavaghan
authors.forename: Blanca
authors.initials: B
authors.lastname: Rodriguez
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004554:Electric Countershock; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular