Work Performance in Failing Myocardium Assessed in a Mathematical Model of the Human Ventricular Myocyte Electromechanical Coupling

Ventricular contraction cycle is characterized by specific scenario of the mechanical loading, which in experiments with the heart muscles/myocytes is mimicked by a work-loop mode of the myocardium twitch. We used recently developed electromechanical model of human ventricular cardiomyocyte to simulate its action potential generation, intracellular calcium dynamics and mechanical activity during work-loop twitches under different afterloads in normal and failing myocardium. The model reproduces well the changes in the force development and shortening observed in experiment with normal and failing human left ventricular wall preparations. The model was also used to predict and explain concomitant changes in action potential generation and calcium transient time course. We also calculated the useful work performed by the virtual muscle in normal and failing myocardium revealing that decrease in sarcoplasmic reticulum calcium content during heart failure may underlie the decrease in myocardial work.