Population of human ventricular cell models calibrated with in vivo measurements unravels ionic mechanisms of cardiac alternans

Cardiac alternans is an important risk factor in cardiac physiology, and is related to the initiation of arrhythmia in a number of pathological conditions. However, the mechanisms underlying the generation of alternans remain unclear. In this study, we used a population of computational models of human ventricular electrophysiology based on the O'Hara-Rudy dynamic model to explore the effect of 11 key factors experimentally reported to be related to cardiac alternans. In vivo experimental datasets obtained from patients undergoing cardiac surgery were used in the calibration of an in silico population of models. The calibrated models in the population were divided into two groups (Normal and Alternans) depending on the occurrence of the alternans. Our results showed that there were significant differences in the following 6 ionic currents between the two groups: the fast sodium current, the L-type calcium current, the rapid delayed rectifier potassium current, the sodium calcium exchanger current, the sarcoplasmic reticulum (SR) calcium release flux, and the SR calcium reuptake flux.