Blocking Na1.8 regulates atrial fibrillation inducibility and cardiac conduction after myocardial infarction.

Abstract

BACKGROUND: The role of Na1.8 impacts in atrial fibrillation susceptibility after myocardial infarction remains only partially understood. We studied the effect of blocking Na1.8 in the cardiac ganglionated plexi (GP) on the atrial fibrillation inducibility and cardiac conduction in the myocardial infarction model. METHODS: Eighteen male beagles were randomly enrolled. Left anterior descending coronary artery was ligated to created myocardial infarction model. Four weeks after surgery, Na1.8 blocker A-803,467 (n = 9) or DMSO (n = 9, control) was injected into the four cardiac major GPs. Sinus rate, ventricular rate during atrial fibrillation, PR interval, atrial effective refractory period, atrial fibrillation duration and the cumulative window of atrial vulnerability were measured before and 60 min after A-803,467 injection. RESULTS: Administration of A-803,467 significantly increased sinus rate, shortened PR interval and increased ventricular rate during atrial fibrillation compared to control. A-803,467 also significantly shortened atrial effective refractory period, prolonged atrial fibrillation duration and increased the cumulative window of atrial vulnerability. A-803,467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, which was used as the surrogate marker for GP function. Double staining of ChAT and Na1.8 demonstrated colocalization of ChAT and Na1.8 in canine GPs. CONCLUSIONS: Blocking Na1.8 in the cardiac GP may modulate atrial fibrillation inducibility and cardiac conduction after myocardial infarction, and the underlying mechanism may be associated with the regulation of the neural activity of the cardiac GP.