Efficacy of diltiazem in two experimental feline models of sudden cardiac death.

The potential role of calcium entry blockers in the prevention of life-threatening arrhythmias associated with acute myocardial ischemia and reperfusion is still controversial. In 98 anesthetized cats, the effect of diltiazem was examined in two experimental models. In protocol I, ventricular tachycardia or fibrillation was consistently induced by the interaction between a 2 minute coronary artery occlusion and a 30 second left stellate ganglion stimulation. After three trials under control conditions, if the same pattern of arrhythmia was induced, the drug under study was administered and three additional trials were performed. In 16 animals the administration of saline solution did not modify the pattern of arrhythmias. In contrast, diltiazem (0.1 mg/kg body weight plus 0.2 mg/kg per h) abolished both ventricular tachycardia and fibrillation that had occurred in 64 and 36%, respectively, of the cats in the control state. In protocol II, a 20 minute coronary artery occlusion was released in three groups; one served as the control group, one received diltiazem 15 minutes before occlusion and one received diltiazem 3 minutes before reperfusion. The incidence of reperfusion ventricular fibrillation was 62% (16 of 26) in the control group. It was significantly (p less than 0.05) reduced by diltiazem administered before the occlusion to 25% (4 of 16), whereas it was not affected when diltiazem was administered just before reperfusion (7 [47%] of 15). These results indicate that diltiazem exerts a striking protective effect against the malignant arrhythmias induced by the combination of acute myocardial ischemia and sympathetic hyperactivity. Diltiazem was also effective in reducing the incidence of life-threatening reperfusion arrhythmias