A Novel In Silico Electromechanical Model of Human Ventricular Cardiomyocyte

Contractility has become one of the main readouts in computational and experimental studies on cardiomyocytes. Following this trend, we propose a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, by coupling a recent human contractile element to the BPS2020 model of electrophysiology. BPSLand is the result of a hybrid optimization process and it reproduces all the electrophysiology experimental indices captured by its predecessor BPS2020, simultaneously enabling the simulation of realistic human active tension and its potential abnormalities. The transmural heterogeneity in both electrophysiology and contractility departments was simulated consistent with previous computational and in vitro studies. Furthermore, our model could capture delayed afterdepolarizations (DADs), early afterdepolarizations (EADs), and contraction abnormalities in terms of aftercontractions triggered by either drug action or special pacing modes. Finally, we further validated the mechanical results of the model against previous experimental and in silico studies, e.g., the contractility dependence on pacing rate. Adding a new level of applicability to the normative models of human cardiomyocytes, BPSLand represents a robust, fully-human in silico model with promising capabilities for translational cardiology.

Automated summary

In this study, a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, is proposed. The model successfully reproduces realistic human active tension and its potential abnormalities, as well as captures the transmural heterogeneity in both electrophysiology and contractility. The model also demonstrates capabilities in simulating various contraction abnormalities. The mechanical results of the model are validated against previous experimental and in silico studies.