Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Experiments on animal hearts (rat, rabbit, guinea pig, etc.) showed that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation. This is because they adjust cardiomyocyte contractile function to various mechanical loads and to the mechanical interaction of heterogeneous myocardial segments in the ventricle walls. In the in vitro experiments on these animals MCF and MEF manifested themselves in several basic classic phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, simultaneous study of electrical, calcium, and mechanical activity of the human heart muscle in vitro is extremely difficult. Here we apply mathematical modeling to study these phenomena. We develop a novel model describing electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. This model combines the 9ten Tusscher - Panfilov9 electrophysiological model of the human cardiomyocyte with our module of the myocardium mechanical activity taken from the 9Ekaterinburg - Oxford9 model and adjusted to human data. Using it we model isometric and isotonic twitches and study effects of MCF and MEF on the excitation-contraction coupling. We have shown that MCF and MEF both for smaller afterloads as compared to bigger ones and for various mechanical interventions during isometric and isotonic twitches substantially affect durations of calcium transient and action potential in the human cardiomyocyte model.