Reperfusion-induced arrhythmias in the conscious rat: a comparative study with three calcium antagonists

The effects of three calcium antagonists (diltiazem, verapamil, and nifedipine) on reperfusion-induced arrhythmias were compared in a conscious rat preparation with coronary artery occlusion and implanted electrocardiogram limb electrodes. Upon reperfusion after a 5-min period of occlusion, all (15/15) untreated control rats exhibited immediate ventricular tachycardia, which rapidly deteriorated to ventricular fibrillation; 87% (13/15) of the rats died as a consequence of these rhythm disturbances. In the groups treated with calcium antagonists, each drug (diltiazem, verapamil, or nifedipine) was given as an intravenous bolus 10 min prior to coronary occlusion (n = 12 in each group). The incidence of ventricular fibrillation was significantly reduced by all three calcium antagonists and this antifibrillatory effect resulted in a significantly lower mortality in all drug-treated groups. With diltiazem (0.5 and 2.0 mg/kg) mortality fell from 87 to 42% (P less than 0.05) and 35% (P less than 0.01), respectively; with verapamil (0.5 and 5.0 mg/kg) it fell to 25% (P less than 0.01) and 0% (P less than 0.001); and with nifedipine (5.0 and 50 micrograms/kg), it fell to 25% (P less than 0.01) and 8% (P less than 0.001). At a dose of 5.0 mg/kg, verapamil caused a large reduction in heart rate both prior to and during coronary occlusion and reperfusion; however, with other doses and drugs no significant changes in heart rate were observed. ST segment elevation during the 5-min ischemic period was reduced by pretreatment with all drugs. In conclusion, in the conscious rat, pretreatment with diltiazem, verapamil, or nifedipine affords some protection against reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)