A Framework for Modeling of Mechano-Electrical Feedback Mechanisms of Cardiac Myocytes and Tissues

The term cardiac mechano- electrical feedback precis the various phenomena related to modulation of electrophysiology by mechanical deformation of cells and tissues of the heart. The significance of mechano-electrical feedback and the underlying mechanisms are still poorly understood despite intense experimental research. We introduce and discuss a framework for computational modeling and simulation of mechano-electrical feedback at ion channel, cell and tissue level. The framework consists of modules to reconstruct electrical currents through mechano-sensitive ion channels, their effect on myocytes' electrophysiology, strain- modulation of tissue conductivities and electrical conduction in myocyte clusters and myocardium. We applied the framework to study the effect of strain on conduction velocity in papillary muscle. The simulations reconstructed strain-conduction velocity relationships as reported in experimental studies. Furthermore, the computational studies indicated that increased stimulus frequency aggravated the reduction of conduction velocity for larger strains. Mathematical modeling of mechano-electrical feedback will help to integrate experimental data and predict behavior at system level. Computational simulations might give otherwise unavailable insights, particularly with respect to clinical relevance of mechano- electrical feedback.