Recently we demonstrated that vagal stimulation increases ventricular fibrillation threshold (VFT) and decreases the incidence of spontaneous ventricular fibrillation during acute coronary occlusion. Assuming this protective effect of the vagus to be mediated through acetylcholine release, we hypothesized that inhibition of acetylcholinesterase, a potential clinical intervention, would also enhance electrical stability of acutely ischemic myocardium. A balloon cuff was placed around the left

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... erior descending coronary artery (LAD) and left ventricular and atrial electrodes were implanted in 10 dogs. Five to seven days later VFT was determined (VFT was defined as the minimum current required to produce ventricular fibrillation). During nonischemic conditions VFT was 42 ± 8 ma; when edrophonium was infused (1-2 mg/kg/min), VFT increased to 77 + 11 ma (P < 0.005). During ischemia induced by LAD occlusion VFT fell to 19 ± 4 ma. Edrophonium increased VFT during ischemia to 52 ± 13 ma (P < 0.005), a level not significantly different from preischemic values. These results suggest that enhanced electrical stability of ventricular myocardium produced by vagal stimulation is mediated by acetylcholine release, and that inhibitors of acetylcholinesterase may provide a new means of therapy for arrhythmias occurring during acute myocardial ischemia.