Modelling Effect of Heart Failure on the Electrical Activity of Sheep Atria

Abstract

Heart failure (HF) is associated with cardiac arrhythmias, which impairs cardiac electromechanics that causes dysfunction of cardiac muscle contraction leading to increased risks of morbidity and mortality. Previous studies have revealed that HF causes alteration to the electrophysiological and structural properties of the atria. The aim of this study was to investigate the primary factor of HF-induced remodelling on the dynamical behaviours of electrical excitation waves in sheep atria. The biophysically detailed model of sheep atrial action potentials developed by Butters et al was modified to incorporate experimental data of HF-induced remodelling on ion channels. The developed atrial cell models in HF were then incorporated into the 3D anatomical sheep atria model developed in our previous study. The 3D model considered both electrical heterogeneity and tissue anisotropy. At the cellular level, HF shortened the action potential duration at 90% of repolarisation (APD90). At 3D organ level, activation time of the whole atria was prolonged due to the downregulation of expression of gap junction proteins (Cx43). Consequently, the wavelength of excitation waves was abbreviated, which may help to sustain re-entrant excitation waves in the atria. This study provides mechanistic insights into the pro-arrhythmic effect of HF-induced remodeling on ion channels, Ca2+ handling and intercellular coupling in the sheep atria.