title: Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation.
abstract: Mechanisms underlying the genesis of re-entrant substrate for the most common cardiac arrhythmia, atrial fibrillation (AF), are not well understood. In this study, we develop a multi-scale three-dimensional computational model that integrates cellular electrophysiology of the left atrium (LA) and pulmonary veins (PVs) with the respective tissue geometry and fibre orientation. The latter is reconstructed in unique detail from high-resolution (approx. 70 μm) contrast micro-computed tomography data. The model is used to explore the mechanisms of re-entry initiation and sustenance in the PV region, regarded as the primary source of high-frequency electrical activity in AF. Simulations of the three-dimensional model demonstrate that an initial break-down of normal electrical excitation wave-fronts can be caused by the electrical heterogeneity between the PVs and LA. High tissue anisotropy is then responsible for the slow conduction and generation of a re-entrant circuit near the PVs. Evidence of such circuits has been seen clinically in AF patients. Our computational study suggests that primarily the combination of electrical heterogeneity and conduction anisotropy between the PVs and LA tissues leads to the generation of a high-frequency (approx. 10 Hz) re-entrant source near the PV sleeves, thus providing new insights into the arrhythmogenic mechanisms of excitation waves underlying AF.
authors.affiliation: Department of Biomedical Engineering , King's College London , London , UK.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Aslanidi
authors.affiliation: School of Physics & Astronomy , University of Manchester , Manchester , UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Colman
authors.affiliation: Department of Biomedical Engineering , King's College London , London , UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Varela
authors.affiliation: Auckland Bioengineering Institute , University of Auckland , Auckland , New Zealand.
authors.forename: Jichao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Auckland Bioengineering Institute , University of Auckland , Auckland , New Zealand.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Smaill
authors.affiliation: School of Physiology & Pharmacology , University of Bristol , Bristol , UK.
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.affiliation: Faculty of Medical & Human Sciences , University of Manchester , Manchester , UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Boyett
authors.affiliation: School of Physics & Astronomy , University of Manchester , Manchester , UK.
authors.forename: Henggui
authors.initials: H
authors.lastname: Zhang
keywords: cardiac arrhythmias; integrative modelling; re-entrant waves