Comparison of effects of verapamil and those of nicardipine on myocardial ischemia and reperfusion injury: a study in an in situ rabbit model]

This study was designed to investigate whether two L-type calcium antagonists, verapamil and nicardipine reduce the myocardial necrosis (infarct size) following ischemia and reperfusion. Rabbits (n = 52) were subjected to regional myocardial ischemia by 30 min of the left anterior descending artery occlusion followed by 3 hrs of reperfusion under ketamine/xylazine anesthesia. The animals were randomly assigned to a control group, and verapamil or nicardipine treatment groups. A continuous infusion of verapamil (0.1 mg.kg-1.h-1) or nicardipine (0.06 mg.kg-1.h-1) was initiated 5 min prior to ischemia, immediately after ischemia, 5 min after ischemia, 5 min prior to reperfusion, immediately after reperfusion, and 5 min after reperfusion. A lead II ECG was recorded throughout the experiment for determining ventricular arrhythmias. The area at risk was delineated by Evans blue, and infarct size was determined by triphenyl tetrazolium chloride staining at the end of the experiment in the heart (the left anterior descending artery was religated). The area at risk showed no significant differences among all the groups tested; infarct size in the rabbits to which verapamil was given 5 min before subjecting to ischemia was significantly reduced to 41.7 +/- 4.3% from 65.9 +/- 1.7% in control rabbits. The treatment with nicardipine at any period of time did not reduce infarct size. On the other hand, the incidence of reperfusion-induced arrhythmias was decreased by nicardipine infusion, when started 5 min prior to ischemia, immediately after ischemia, 5 min after ischemia, 5 min prior to reperfusion, and immediately after reperfusion. These results suggest that verapamil given before coronary artery occlusion has an infarct limiting effect in the myocardium, and that nicardipine has an antiarrhythmic effect during reperfusion in the rabbit heart.