Development of ventricular tachyarrhythmias in the conscious canine during the recovery phase of experimental ischemic injury: effect of bethanidine administration.
The antiarrhythmic and antifibrillatory actions of bethanidine were evaluated in two conscious canine models which are capable of developing ventricular tachyarrhythmias during the recovery phase of myocardial infarction. In the first model, nonsustained (n = 3) or sustained (n = 12) ventricular tachycardia (cycle length, 165 +/- 6 ms; mean +/- SD) was initiated by programmed electrical stimulation, 4-9 days after experimental myocardial infarction. Bethanidine was administered in cumulative doses of 2, 4, 8, and 16 mg/kg and programmed stimulation repeated. Bethanidine, in doses of 4, 8, and 16 mg/kg, slowed the cycle length of the tachycardia and allowed slower rates of ventricular pacing to produce equivalent delays at epicardial sites in the ischemic zone. Despite these changes, induction of sustained ventricular tachycardia was prevented in only two of 13 animals. Bethanidine (8 mg/kg i.v. every 8 h, n = 4; 16 mg/kg i.v. every 8 h, n = 5) failed to prevent the development of premature ventricular beats, ventricular tachycardia, and ventricular fibrillation which developed in response to a transient ischemic episode superimposed on the heart that had a previous acute myocardial infarction. No differences in survival at 24 h were observed between saline- (10%, n = 10) and bethanidine-treated (0%, n = 9) groups. These results suggest that bethanidine acts to increase the refractory period and depresses conduction velocity in ischemically injured tissue, slowing the rate of ventricular tachycardia. However, the drug fails to suppress the development of ventricular arrhythmias and ventricular fibrillation in both canine models.
D000818:Animals; D001627:Bethanidine / Q000494:pharmacology / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006146:Guanidines / Q000627:therapeutic use*; D006321:Heart / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D006146:Guanidines; D001627:Bethanidine