Analysis and improvement of a human ventricular cell model for investigation of cardiac arrhythmias

The use of experiments for studying cardiac arrhythmias, the effect of drugs, or pathologies on cardiac electrophysiology is very limited. This has made mathematical modeling and simulation of heart´s electrical activity a fundamental tool to understand cardiac behavior. In this study several modifications were introduced to a recently proposed human ventricular cell model. Four stimulation protocols were applied to the original and improved models of isolated cell, and a number of cellular arrhythmic risk biomarkers were computed: steady-state action potential (AP) and [Ca²⁺] transient properties, AP duration (APD) restitution curves, APD adaptation to abrupt changes in heart rate, and intracellular [Ca²⁺] and [Na⁺] rate dependence. Our modifications led to: a) further improved AP triangulation (78.1 ms); b) APD rate adaptation curves characterized by fast and slow time constants within physiological ranges (10.1 s and 105.9 s); c) maximum S1S2 restitution slope in accordance with experimental data (S_S1S2 = 1.0).