Investigation of the Electrophysiological Remodelling in Acute and Chronic Post-Myocardial Infarction

Abstract

Sudden cardiac death was reported in both the acute stage and the chronic heart failure (HF) stage after myocardial infarction (MI). The goal of this study is to investigate the pro-arrhythmic cellular effects of post-MI electrophysiological remodelling for both the acute stage and the chronic stage, using human-based computer modelling and simulation. The ToR-ORd human ventricular cellular model was used as baseline, and a new formulation of the calcium activated potassium current was also included in order to reflect its enhanced expression in the HF stage. We constructed and calibrated populations of human ventricular cell models to represent electrophysiological variability of normal zone (NZ) myocytes. For the acute post-MI stage, three types of border zone (BZ) ionic remodelling were considered based on canine experimental data. For the chronic phase with the development of HF, ionic remodelling in BZ and the remote zone (RZ) were introduced based on minipig and human experiments. For both the acute stage and the chronic stage post-MI, simulations showed that both large and small pro-arrhythmic dispersion in action potential duration can be present between BZ and non-infarcted NZ or RZ, and the post-MI ionic remodelling led to weak calcium transient in the BZ.