title: Transmural electrophysiological heterogeneities in action potential duration increase the upper limit of vulnerability.
abstract: Transmural dispersion in action potential duration (APD) has been shown to contribute to arrhythmia induction in the heart. However, its role in termination of lethal arrhythmias by defibrillation shocks has never been examined. The goal of this study is to investigate how transmural dispersion in APD affects cardiac vulnerability to electric shocks, in an attempt to better understand the mechanisms behind defibrillation failure. This study used a three- dimensional, geometrically accurate finite element bidomain rabbit ventricular model. Transmural heterogeneities in ionic currents were incorporated based on experimental data to generate the transmural APD profile recorded in adult rabbits during pacing. Results show that the incorporation of transmural APD heterogeneities in the model causes an increase in the upper limit of vulnerability from 26.7 V/cm in the homogeneous APD ventricles to 30.5 V/cm in the ventricles with heterogeneous transmural APD profile. Examination of shock-end virtual electrode polarisation and postshock electrical activity reveals that the higher ULV in the heterogeneous model is caused by increased dispersion in postshock repolarisation within the LV wall, which increases the likelihood of the establishment of intramural re-entrant circuits.
authors.affiliation: Computing Laboratory, Oxford, UK. thum@comlab.ox.ac.uk
authors.forename: T
authors.initials: T
authors.lastname: Maharaj
authors.forename: B
authors.initials: B
authors.lastname: Rodriguez
authors.forename: R
authors.initials: R
authors.lastname: Blake
authors.forename: N A
authors.initials: NA
authors.lastname: Trayanova
authors.forename: D J
authors.initials: DJ
authors.lastname: Gavaghan
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology* / Q000628:therapy; D004195:Disease Models, Animal; D004554:Electric Countershock; D004594:Electrophysiology / Q000379:methods; D007700:Kinetics; D008955:Models, Cardiovascular; D011817:Rabbits; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000628:therapy