Electro-Mechanical Coupling in Human Atrial Cardiomyocytes: Model Development and Analysis of Inotropic Interventions

Human-based computational models are a powerful tool that complements the experimental approaches and can improve our understanding of individual components of the heart by integrating them into one system. This paper aims to couple and calibrate a human atrial electro-mechanical model to analyse the coupling effects and inotropic interventions on human atrial electrophysiology, calcium dynamics, and active isometric contraction on a cellular scale. A human atrial electrophysiology model was coupled with one of the recently developed biophysically detailed contraction models. A collection of human atrial experimental data has been presented to calibrate the coupled model. The calibrated electro-mechanical human atrial model yielded action potential, calcium transient and active tension that were validated against the experiments and conclusions were drawn to explain the mismatch between in-silico and in-vitro experiments on inotropic interventions. The coupled and calibrated human atrial electro-mechanical model and simulation framework developed in this study serves as a pathway for future investigations of the effect of contractile performance and inotropic interventions on the electrophysiology of the atria.