Prevention of ventricular fibrillation by bretylium in a conscious canine model of sudden coronary death

Abstract

In anesthetized dogs, a silver wire electrode was inserted into the lumen of the circumflex coronary artery (LCX) and myocardial infarction was produced by a temporary 90-minute occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Four days later while in the ambulatory state, a 150 μA current was applied to the intimal surface of the LCX of saline (n = 10) and bretylium (n = 10) treated animal. Intimal injury and coronary thrombosis produced ST segment changes at 138 ± 39 minutes (χ ± SEM), followed by premature ventricular beats (at 142 ± 37 minutes), ventricular tachycardia (at 156 ± 49 minutes), and ventricular fibrillation (at 163 ± 51 minutes) in 9 of 10 saline-treated animals. In bretylium-treated animals, ST segment changes appeared at 128 ± 35 minutes, with six animals surviving for 24 hours ( p < 0.03 vs saline). LAD infarction was present in both saline (14.1 ± 2.3%) and bretylium (15.1 ± 2.1% of left ventricle) treated animals with only bretylium-treated animals developing LCX infarcts (16.1 ± 2.1%). Bretylium prevents ventricular fibrillation (VF) resulting from ischemia at a site distant to prior myocardial infarction in the conscious dog and deserves further attention as a potential antifibrillatory agent for prevention of sudden coronary death in man.