Computational modeling of the electromechanical response of a ventricular fiber affected by eccentric hypertrophy

The aim of this work is to study the effects of eccentric hypertrophy on the electromechanics of a single myocardial ventricular fiber by means of a one-dimensional finite-element strongly-coupled model. The electrical current ow model is written in the reference configuration and it is characterized by two geometric feedbacks, i.e. the conduction and convection ones, and by the mechanoelectric feedback due to stretchactivated channels. First, the influence of such feedbacks is investigated for both a healthy and a hypertrophic fiber in case of isometric simulations. No relevant discrepancies are found when disregarding one or more feedbacks for both fibers. Then, all feedbacks are taken into account while studying the electromechanical responses of fibers. The results from isometric tests do not point out any notable difference between the healthy and hypertrophic fibers as regards the action potential duration and conduction velocity. The length-tension relationships show increased stretches and reduced peak values for tension instead. The tension-velocity relationships derived from afterloaded isotonic and quick- release tests depict higher values of contraction velocity at smaller afterloads. Moreover, higher maximum shortenings are achieved during the isotonic contraction. In conclusion, our simulation results are innovative in predicting the electromechanical behavior of eccentric hypertrophic fibers.

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation–contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation–contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.