Evolution of the Seminal O'Hara Rudy Model to More Accurately Simulate the Electrophysiology of Human Ventricular Cardiomyocytes

The aim of our work consists in developing a new model of the human ventricular cardiomyocyte, based on the O'Hara-Rudy model (ORd), to improve, in particular, the action potential duration (APD) dependence on the extracellular Ca²⁺ concentration (Ca_o). Moreover, the new model reproduces all the available experimental data on APD rate dependence, APD restitution, drug block effects, etc., when the experimental extracellular ionic concentrations are carefully reproduced in simulationsThe main differences between our and the ORd model are: a novel Markovian formulation for the L-type Ca²⁺ current; the Markovian rapid delayed rectifier K⁺ current formulation published by Li et al.; a new formulation of the Ca²⁺ release from the sarcoplasmic reticulum. Several model parameters were modifiedOur BS (Bartolucci-Severi) model successfully improved the ORd, one of the most detailed, used and influent models in computational cardiology, by reproducing the APD-Ca_o relationship while keeping all the original model features tested in the appropriate experimentally-matched conditions. Furthermore, the BS was suitability as baseline for the generation of in silico populations of models and for reproducing cardiac abnormalities such as early afterdepolarizations.