Disruption of cardiac vagal nerve terminal function in the ischemic myocardium

Abstract

Purpose: Despite the importance of vagal efferent activity during acute myocardial ischemia (AMI) such as an antifibrillatory effect, changes in the endogenous acetylcholine (ACh) release in the ischemic myocardium remain unknown. We examined whether AMI disrupted vagal nerve terminal function. Methods: In anesthetized cats, a dialysis probe was implanted into the left ventricular free wall. The ACh content in the dialysate was measured as an index of myocardial interstitial ACh level. We examined the effects of AMI induced by a left anterior descending coronary artery occlusion on myocardial ACh release in cats with and without vagotomy. In different cats with vagotomy, we examined the effects of Na⁺ channel blocker (tetrodotoxin), intracellular Ca²⁺ antagonist (3,4,5-trimethoxybenzoic acid 8-(dietyl amino)-octyl ester), N-type Ca²⁺ channel blocker (ω-conotoxin GVIA), L-type Ca²⁺ channel blocker (verapamil), P/Q-type Ca²⁺ channel blocker (ω-conotoxin GVIIC), and Na⁺/Ca²⁺ exchange inhibitor (KB7943). Results: AMI increased myocardial ACh level from 0.68±0.12 to 12.3±3.3 nM (mean±SE, P<0.01). Vagotomy did not inhibit the ACh release. Inhibition of intracellular Ca²⁺ mobilization suppressed the ACh release (4.4±0.9 nM). None of Na⁺ channel blockade, N-, L-, P/Q-type Ca²⁺ channel blockade, and Na⁺/Ca²⁺ exchange inhibition suppressed the ACh release. Conclusion: AMI increased myocardial ACh release in the ischemic myocardium via the intracellular Ca²⁺ mobilization. [Jpn J Physiol 54 Suppl:S61 (2004)]