In this study we examined the cardiovascular and possible antiarrhythmic actions of
anipamil, a long acting analog of
verapamil. Initial dose-response studies for
anipamil (0.25-6.0 mg/kg, i.v.) in
pentobarbitone-anesthetized pigs (n = 4) were conducted to determine the effects of the
drug on EKG and hemodynamic measures. In this initial study
anipamil was found to produce a dose-dependent reduction in blood pressure, left-ventricular pressure and its derivative (dP/dtmax), cardiac output, and increase in heart rate. These results were used as a basis from which to choose doses for a second study to assess antiarrhythmic actions of
anipamil against arrhythmias induced by regional
myocardial ischemia. The antiarrhythmic effects of the two doses were compared with
verapamil when the latter was given at a dose producing cardiovascular effects mid-way between those produced by the two doses of
anipamil. Anesthetized pigs were randomly assigned to receive one of three
drug treatments, or vehicle control, prior to occlusion of the left-anterior descending coronary artery. Antiarrhythmic effectiveness of low (1.0 mg/kg + 0.10 mg/kg/min infusion, n = 8) and high (5.0 mg/kg + 0.50 mg/kg/min infusion, n = 12) dose
anipamil was compared to that of
verapamil (0.5 mg/kg + 0.60 mg/kg/min infusion, n = 8) in a vehicle controlled study (n = 15). Arrhythmic events (VPB, VT and VF incidence) were monitored and grouped according to their time of occurrence after occlusion. Thus phase 1a arrhythmias occurred 0-5 min after initiation of occlusion, phase 1b, 5-30 min, and phase 2, 0.5-4 hr after occlusion. This study showed that during phase 1a there was a low incidence of arrhythmias in all groups except the one receiving 5 mg/kg
anipamil where the group incidence of VT was 58% as compared to 20% in controls (n = 15). Most ventricular arrhythmias occurred in all groups during phase 1b. In this phase
verapamil abolished VF and reduced VT, as compared with controls.
Anipamil (high and low doses) tended to reduce VT but not VF. In the period 0.5 to 4 hours post occlusion (phase 2) all three
drug treatments were associated with fewer arrhythmias but this only reached statistical significance with
verapamil. Thus
verapamil was more efficacious than
anipamil at providing antiarrhythmic protection against both early and late onset arrhythmias.
Anipamil may have been proarrhythmic in the early phase of arrhythmias and only moderately antiarrhythmic, if at all, in the later phase.(ABSTRACT TRUNCATED AT 400 WORDS)