The antifibrillatory properties of UM-272 (dimethylpropranolol; Pranolium) were evaluated in a conscious canine model of sudden coronary death. The initial preparation of the animal model was carried out under surgical anesthesia and involved the intraluminal implantation of a Teflon-coated silver wire into the circumflex coronary artery so that 3 mm of the bared electrode was in contact with the endothelial surface. The left anterior descending coronary artery then was occluded for a period of 90 min and reperfused in the presence of a critical stenosis. Three days after myocardial infarction, they were randomized into two groups. One group (n = 10) served as controls and received saline. The second group (n = 10) received UM-272 in a dose of 5 mg/kg every 6 h. On day 4, a 150 microA current was applied to the intimal surface of the left circumflex coronary artery, resulting in transient or permanent alterations in circumflex coronary blood flow accompanied by electrocardiographic evidence of regional myocardial ischemia. The time to onset of ST-segment changes in the saline control group was 99 +/- 34 min and was followed by the appearance of premature ventricular complexes (111 +/- 34 min) and subsequent ventricular tachycardia (131 +/- 37 min) which terminated in ventricular fibrillation in each of the 10 dogs. Animals treated with UM-272 likewise developed ST-segment changes (156 +/- 28 min) and premature ventricular complexes (168 +/- 29 min), but 4 of 10 animals failed to develop ventricular fibrillation (P less than 0.05 vs. saline). These results demonstrate that UM-272, the dimethyl quaternary analog of propranolol, is effective in reducing the incidence of ventricular fibrillation in a conscious canine model in which the superimposition of a transient ischemic event upon an already jeopardized heart leads to the development of sudden death.
Animals Anti-Arrhythmia Agents