Mechano-electrical coupling explains worsening of cardiac function in the asynchronous heart

Asynchronous activation of the ventricles deteriorates cardiac function acutely, followed by further worsening over time. In a multi-scale model we tested the hypothesis that the second phase is due to mechano-electrical coupling (MEC), mediated by remodeling of ionic membrane currents. Our model describes hemodynamic interaction between the left and right ventricle as well as mechanical interaction of three wall segments. At cellular level, excitation-contraction coupling is described by a cascade of physiological models. At the organ level, pressure-volume relations are obtained by simulating the pulmonary and systemic circulation. MEC is incorporated by local adaptation of L-type Ca²⁺ current to local mechanical load. Our model predicts that MEC has no effect on cardiac function in the heart with normal conduction, but leads to reduced pump function in the asynchronous heart. We conclude that MEC may aggravate the consequences of abnormal electrical activation in the long run.