Chronic ventricular tachyarrhythmias in the conscious dog: prevention by UM-272 (dimethylpropranolol).
The ability of chronic UM-272 (dimethylpropranolol) treatment to prevent the induction of reentrant ventricular tachyarrhythmias was assessed in the conscious dog subjected to serial programmed electrical stimulation on days 3--5 after myocardial infarction. In 20 untreated control animals, programmed electrical stimulation produced nonsustained ventricular tachycardia in 6 animals (30%), sustained ventricular tachycardia in 8 animals (40%), and ventricular fibrillation in 6 animals (30%) on the third day after occlusion and reperfusion of the left anterior descending coronary artery. On day 4, programmed electrical stimulation produced nonsustained ventricular tachycardia in 5 animals (36%), sustained ventricular tachycardia in 7 animals (50%), and ventricular fibrillation in 2 animals (14%). UM-272, 5 or 10 mg/kg, i.v., was administered every 12 hr to a separate group of 8 dogs after the induction of ischemic myocardial injury. Programmed electrical stimulation on day 3 after myocardial infarction failed to elicit ventricular arrhythmias in 4 animals (50%, p = 0.014), with acute administration of the next UM-272 dose preventing the induction of ventricular tachyarrhythmias in 7 animals (88%, p less than 0.0001). On day 4, programmed electrical stimulation failed to elicit ventricular arrhythmias in 5 aminals (63%, p = 0.0021). Thirty-six hours after the withdrawal of UM-272, programmed electrical stimulation produced ventricular fibrillation in 5 animals (63%) and sustained ventricular tachycardia which degenerated to ventricular fibrillation in 3 animals (37%). UM-272 significantly (p less than 0.05) depressed conduction in both normal and ischemically injured myocardium while also increasing (p less than 0.05) ventricular effective refractory periods. The results of these investigations suggest that UM-272 may be effective in preventing reentrant ventricular rhythms in hearts subjected to chronic myocardial ischemic damage and, therefore, may be of potential value in preventing reentrant ventricular arrhythmias in man.
D000818:Animals; D002908:Chronic Disease; D004285:Dogs; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D011433:Propranolol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000517:prevention & control
C002616:pranolium; D011433:Propranolol