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.