AUTHOR=Wu Yong , Luo Zhongxu , Hu Zhengtao , Lv Kun , Liu Yinhua , Wang Deguo 

TITLE=Optical Activation of the Dorsal Horn of the Thoracic Spinal Cord Prevents Ventricular Arrhythmias in Acute Myocardial Ischemia-Reperfusion Rats

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.753959

DOI=10.3389/fcvm.2022.753959

ISSN=2297-055X

ABSTRACT=Background and objectives: Spinal cord stimulation can prevent myocardial ischemia and reperfusion arrhythmias, but the relevant neurons and mechanisms remain unknown. Thus, this study applied optogenetic techniques to selectively activate glutamatergic neurons at the thoracic spinal cord (T1 segment) for examining the anti-arrhythmia effects during acute myocardial ischemic reperfusion. Methods: Adeno-associated viruses (AAV) carrying channelrhodopsin-2 (ChR2, a blue-light sensitive ion channels) CaMKIIα-hChR2(H134R) or empty vector were injected into dorsal horn of T1 spinal cord. Four weeks later, optogenetic simulation with 473-nm blue laser was applied for 30 minutes. Then, myocardial ischemia-reperfusion model was created by occlusion the the anterior descending coronary artery for ischemia (15 min) and reperfusion (30 min). Cardiac electrical activity and sympathetic nerve activity were assessed continuously. Results: CaMKIIα-hChR2 viral transfection is primarily expressed in glutamatergic neurons in spinal cord. Selective optical stimulation the T1 dorsal horn in ChR2 rat reduced ventricular arrhythmia and arrhythmia score during myocardial ischemia–reperfusion, prevented the over-activation of cardiac sympathetic nerve activity during. Additionally, optical stimulation also reduced action potential duration at the 90% level (APD90) and APD dispersion. Conclusion: Selective optical stimulation T1 glutamatergic neurons of dorsal horn prevent ischemia–reperfusion arrhythmias. The mechanism may be associated with inhibiting sympathetic nervous system overexcitation and increasing APD dispersion during myocardial ischemia-reperfusion.