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

Xin Zhou, Jakub Tomek, Blanca Rodriguez
University of Oxford


The incidence of sudden cardiac death (SCD) was reported to be highest in the early period after a myocardial infarction (MI), followed by a progressive decline to a plateau after a few months. Ventricular tachyarrhythmia accounts for about 50% of these SCD. The goal of this study is to investigate the pro-arrhythmic 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 heart failure (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 collected within one week post-MI. For the chronic phase with the development of HF, ionic remodelling in BZ and the remote zone (RZ) were introduced based on minipig experiments after 5 months post-MI with HF development. Finally, another type of RZ remodelling was introduced based on human experimental data from failing hearts.

For both the acute stage and the chronic stage post-MI, simulations report that both large and small pro-arrhythmic dispersion in action potential duration (APD) can be present in post-MI hearts depending on the phase and ionic remodelling present. The biggest APD dispersions were induced by the acute stage BZ ionic remodelling, which is consistent with the higher arrhythmic risk in the acute stage. Post-MI ionic remodelling led to weak calcium transient in the BZ for both the acute stage and the chronic stage, which could affect the stretch-induced alterations in the BZ.