Prevention of ventricular fibrillation by bretylium in a conscious canine model of sudden coronary death.
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 microA current was applied to the intimal surface of the LCX of saline (n = 10) and bretylium (n = 10) treated animals. Intimal injury and coronary thrombosis produced ST segment changes at 138 +/- 39 minutes (chi +/- 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 less than 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.
D000818:Animals; D001949:Bretylium Compounds / Q000627:therapeutic use*; D001950:Bretylium Tosylate / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D003243:Consciousness; D003645:Death, Sudden; D004285:Dogs; D004562:Electrocardiography; D004567:Electrodes, Implanted; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D012306:Risk; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D001949:Bretylium Compounds; D001950:Bretylium Tosylate