Abstract 14695: Cardiac Optogenetics in Intact Rat Heart for Optical Pacing and Defibrillation in Vivo.

Introduction: Optogenetics is an innovative approach combined with genetic encoding of light sensitive proteins and optical manipulation techniques, which provide a cell-specific, high spatial-temporal, flexible and pain-free resolution for cardiac modulation. Hypothesis: Optogenetics enables optoelectronic conversion which can exhibit diversity modulation of the cardiac rhythm according to the illumination alterations. Methods: Adeno-associated virus (AAV) vectors encoding Channelrhodopsin-2 (ChR2) (AAV9-CAG-hChR2 (H134R)-mCherry) were injected into the rat jugular vein to derive ChR2 expression in the whole heart (n=5). Eight weeks later pulse illumination generated by a 473nm laser was focused on different sites of the heart in a 2mm diameter circle to evoke optical pacing of 1:1 capture. After that ventricular fibrillation was induced by coronary artery ligation and burst stimulation in vivo and continuous illumination of 1 second in 2 times of threshold intensity was located on the infarct area, right ventricle and apex 5 seconds after induced arrhythmia to observe the termination efficacy respectively. Results: Pulse illumination on the right atrium, left and right ventricle, septum and apex succeeded in 1:1 pacing (Figure 1A and 1B). The light capture rate detected on the right ventricular illumination raised with the light intensity and pulse duration as presented in the curve (Figure 1C and 1D). The induced ventricular arrhythmia was terminated as the light continuously illuminated on the infarct zone, right ventricle and apex. The successful termination rate was calculated to be 100% in apex and lower in the other two sites (Figure 1E and 1F). Conclusions: These in vivo evidence suggested that epicardial light irradiation on the ChR2 expression heart achieved different cardiac manipulations according to the different illumination pattern. Optogenetic pacing and defibrillation could provide an alternative strategy for arrhythmia therapy. [ABSTRACT FROM AUTHOR]