Abstract
Introduction
Optogenetics is a low-invasive, flexible and highly selective intervention that enables electrical excitation with light on myocardium overexpressing light-sensitive proteins. Optical illumination can control the simultaneous exciting of the whole myocardium under the spot, which is more conducive to recovery from electrical disturbance to sinus rhythm.
Purpose
We explored optogenetic defibrillation for different illumination parameters how to affect defibrillation rates and the possible mechanism of continuous illumination defibrillation.
Methods
Systemic delivery via right jugular vein injection of (AAV9-CAG-hChR2(H134R)-mCherry) were performed in juvenile SD rats to achieve the light sensitive protein Channelrhodopsin-2 (ChR2) transfer throughout the whole heart. We intubated and ventilated rats, opened chest and recorded the ECG. After ligation of the left anterior descending coronary artery, ventricular arrhythmia was induced by electrical burst stimulation (10v, 50Hz, 2s). Cardiac epicardium illumination with 470nm blue laser was performed to investigate the effects of optogenetic defibrillation and its underlying mechanism. Every heart accepted 30 pulses of 20ms duration on 8Hz to test the light intensity threshold for 1:1 capture. Different illumination modes of multiple light intensity (2,4,8,10,20 times threshold intensity), pulse duration (20, 50, 200, 500 and 1000ms) and illumination position (RV apex, RV, RVOT, septum, LV) were applied in each attempt for 4 repetitions with 1 s interval.
Results
We demonstrated that ventricular arrhythmias could be terminated by illumination of the right ventricle at 20 times threshold intensity in 1s (figure A) with the successful defibrillation rate of 95±2.673% (mean ±SEM; N=7). Herein, the successful optogenetic defibrillation rate was strongly depending on light intensity (N=5, n=50 episodes, p=0.0118) and duration of illumination (N=5, n=50 episodes, p<0.0001) (figure B.C). Notably when there were higher intensity and longer pulse duration, the higher defibrillation rate appeared. There was no significant difference in the defibrillation rate among different illumination positions (N=5, n=25episodes per position, p=0.1177) (figure D). To explore the underlying mechanism of optogenetic defibrillation, we performed the same illumination mode during sinus rhythm in 2 rats (figure E. F. G). We observed that higher light intensity and longer pulse duration were more conducive to induce an episode of higher frequency focal excitement.
Views of optogenetic defibrillation
Conclusions
We demonstrated that optogenetic defibrillation is a highly effective intervention and the possible mechanism is partly attributed to overdrive suppression. We believe that optogenetic approach is potentially to be translated into more efficient and pain-free clinical termination of ventricular arrhythmia.
Acknowledgement/Funding
The national natural science foundation of China (81772044)
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