P6347Wireless optogenetic inhibition of cardiac sympathetic nerve activity to improve cardiac function and remodeling in chronic post-infarction canines

Abstract

Abstract Background Our previous study has shown that optogenetic modulation of left stellate ganglion (LSG) nerve activity suppresses ventricular arrhythmia (VA) after acute myocardial infarction (MI). Objective This study introduced a fully implantable, battery-free wireless optogenetic neuromodulation system to investigate whether chronic optogenetic inhibition of LSG nerve activity could reduce myocardial infarct size and improve left ventricular (LV) function and remodeling in a post-MI canine model. Methods Eighteen beagles were randomized into the normal control group (saline injection without MI, n=6), the MI group (AAV2/9-CAG-GFP injection plus MI, n=6) and the optogenetics group (AAV2/9-CAG-ArchT-GFP injection plus MI, n=6). Four weeks after AAV/saline microinjection into LSG, MI was induced and LED device (Figure 1A) was implanted (Figure 1B, C) to perform illumination (565nm) for optogenetic modulation 1h per day for 4 weeks. Results Chronic optogenetic modulation significantly attenuated LSG function and neural activity as compared to the MI group. Chronic optogenetic modulation significantly reduced myocardial infarction size and improved LV function (LV ejection fraction: 53±1.3% vs. 45.9±1.8%, P<0.05) as compared to the MI group. Furthermore, chronic optogenetic modulation suppressed MI-induced LSG sympathetic remodeling and LV fibrosis. Figure 1 Conclusion Chronic optogenetic modulation using this fully implantable, battery-free wireless optogenetic system significantly inhibited LSG nerve activity, reduced myocardial infarction size, improved LV function and remodeling in a post-MI canine model (Figure 1D).