Models of stretch-activated ventricular arrhythmias

One of the most important components of mechanoelectric coupling is stretch-activated channels, sarcolemmal channels that open upon mechanical stimuli. Uncovering the mechanisms by which stretch-activated channels contribute to ventricular arrhythmogenesis under a variety of pathologic conditions is hampered by the lack of experimental methodologies that can record the 3-dimensional electromechanical activity simultaneously at high spatiotemporal resolution. Computer modeling provides such an opportunity. The goal of this review is to illustrate the utility of sophisticated, physiologically realistic, whole heart computer simulations in determining the role of mechanoelectric coupling in ventricular arrhythmogenesis. We first present the various ways by which stretch-activated channels have been modeled and demonstrate how these channels affect cardiac electrophysiologic properties. Next, we use an electrophysiologic model of the rabbit ventricles to understand how so-called commotio cordis, the mechanical impact to the precordial region of the heart, can initiate ventricular tachycardia via the recruitment of stretch-activated channels. Using the same model, we also provide mechanistic insight into the termination of arrhythmias by precordial thump under normal and globally ischemic conditions. Lastly, we use a novel anatomically realistic dynamic 3-dimensional coupled electromechanical model of the rabbit ventricles to gain insight into the role of electromechanical dysfunction in arrhythmogenesis during acute regional ischemia.