Optogenetic approaches for termination of ventricular tachyarrhythmias after myocardial infarction in rats in vivo.

Cardiac optogenetics facilitates the painless manipulation of the heart with optical energy and was recently shown to terminate ventricular tachycardia (VT) in explanted mice heart. This study aimed to evaluate the optogenetic-based termination of induced VT under ischemia in an open-chest rat model and to develop an optimal, optical-manipulation procedure. VT was induced by burst stimulation after ligation of the left anterior descending coronary artery, and the termination effects of the optical manipulation, including electrical anti-tachycardia pacing (ATP) and spontaneous recovery, were tested. Among different multisegment optical modes, four repeated illuminations of 1000 ms in duration with 1-second interval at a 20-times intensity threshold on the right ventricle achieved the highest termination rate of 86.14% ± 4.145%, higher than that achieved by ATP and spontaneous termination. We demonstrated that optogenetic-based cardioversion is feasible and effective in vivo, with the underlying mechanism involving the light-triggered, ChR2-induced depolarization of the illuminated myocardium, in turn generating an excitation that disrupts the preexisting reentrant wave front.