title: Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study.
abstract: Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK. richard@cbiol.leeds.ac.uk
authors.forename: Richard H
authors.initials: RH
authors.lastname: Clayton
authors.forename: Arun V
authors.initials: AV
authors.lastname: Holden
mesh_terms: D000200:Action Potentials; D016880:Anisotropy; D003198:Computer Simulation; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D008959:Models, Neurological; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac; D009431:Neural Conduction; D017180:Tachycardia, Ventricular / Q000150:complications / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology*