AUTHOR=Qi Baozhen , Dai Shimo , Song Yu , Shen Dongli , Li Fuhai , Wei Lanfang , Zhang Chunyu , Nie Zhenning , Lin Jiaxiong , Cai Lidong , Ge Junbo 

TITLE=Blockade of NaV1.8 Increases the Susceptibility to Ventricular Arrhythmias During Acute Myocardial Infarction

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.708279

DOI=10.3389/fcvm.2021.708279

ISSN=2297-055X

ABSTRACT=<p><italic>SCN10A</italic>/Na<sub>V</sub>1.8 may be associated with a lower risk of ventricular fibrillation in the setting of acute myocardial infarction (AMI), but if and by which mechanism Na<sub>V</sub>1.8 impacts on ventricular electrophysiology is still a matter of debate. The purpose of this study was to elucidate the contribution of Na<sub>V</sub>1.8 in ganglionated plexi (GP) to ventricular arrhythmias in the AMI model. Twenty beagles were randomized to either the A-803467 group (<italic>n</italic> = 10) or the control group (<italic>n</italic> = 10). Na<sub>V</sub>1.8 blocker (A-803467, 1 μmol/0.5 mL per GP) or DMSO (0.5 mL per GP) was injected into four major GPs. Ventricular effective refractory period, APD<sub>90</sub>, ventricular fibrillation threshold, and the incidence of ventricular arrhythmias were measured 1 h after left anterior descending coronary artery occlusion. A-803467 significantly shortened ventricular effective refractory period, APD<sub>90</sub>, and ventricular fibrillation threshold compared to control. In the A-803467 group, the incidence of ventricular arrhythmias was significantly higher compared to control. A-803467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, suggesting that A-803467 could inhibit GP activity. <italic>SCN10A</italic>/Na<sub>V</sub>1.8 was readily detected in GPs, but was not validated in ventricles by quantitative RT-PCR, western blot and immunohistochemistry. While <italic>SCN10A</italic>/Na<sub>V</sub>1.8 is detectible in canine GPs but not in ventricles, blockade of Na<sub>V</sub>1.8 in GP increases the incidence of ventricular arrhythmias in AMI hearts. Our study shows for the first time an influence of <italic>SCN10A</italic>/Na<sub>V</sub>1.8 on the regulation of ventricular arrhythmogenesis via modulating GP activity in the AMI model.</p>