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.