Blocking the Nav1.8 channel in the left stellate ganglion suppresses ventricular arrhythmia induced by acute ischemia in a canine model

Abstract

Abstract Left stellate ganglion (LSG) hyperactivity promotes ischemia induced ventricular arrhythmia (VA). Blocking the Nav1.8 channel decreases neuron activity. Therefore, the present study aimed to investigate whether blocking the Nav1.8 channel with its specific blocker A-803467 in the LSG reduces sympathetic activity and exerts anti-arrhythmic effects. Forty canines were divided into dimethylsulfoxide (DMSO) group and 10 mM, 15 mM, and 20 mM A-803467 groups. A volume of 0.1 ml of A-803467 or DMSO was injected into the LSG. The ventricular electrophysiological parameters, LSG function were measured before and 30 min after the injection. VA was assessed for 60 min after ischemia and then LSG tissues were collected for molecular biological experiments. Compared with DMSO, concentration-dependent prolonged action potential duration and effective refractory period, decreased LSG function were identified after A-803467 treatment. Moreover, the severity of ischemia induced VA was decreased in A-803467 groups. Furthermore, decreased nerve growth factor, decreased c-fos and increased sympathetic neuron apoptosis were found in the LSG after A-803467 injection. In conclusion, blocking the Nav1.8 channel could significantly attenuate ischemia-induced VA, primarily by suppressing LSG activity.