Biochemical and antiarrhythmic effects of three calcium channel antagonists in ischemic canine hearts.

The cardioprotective and antiarrhythmic effects of diltiazem, nilvadipine, and verapamil were evaluated in 33 dogs. The left anterior descending coronary artery (LAD) was occluded for two hours, 25 minutes after saline administration (controls); ten minutes after diltiazem (0.25 mg/kg); 15 minutes after nilvadipine (1 micrograms/kg/min); or ten minutes after verapamil (0.4 mg/kg). Changes in blood pressure and heart rate were monitored throughout the experiment. Two hours after LAD occlusion, mitochondria were prepared from ischemic and nonischemic areas and their function was measured polarographically. Fractionation of myocardial tissue from the ischemic and nonischemic areas was performed and activities of lysosomal enzymes were measured. LAD occlusion induced mitochondrial dysfunction and leakage of lysosomal enzymes in the ischemic area. Administration of the calcium antagonists preserved mitochondrial function and prevented leakage of lysosomal enzymes. All three calcium antagonists reduced the incidence of ventricular arrhythmias during ischemia. The results indicate that calcium may play an important role in the development of biochemical and electrical disturbances during ischemia.