Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium.

TLDR: Hearts from the rabbits treated with propranolol, verapamil or nifedipine were protected against ischemia, and ischemIA with reperfusion-induced decline in the ATP-generating and O 2 -utillzing capacity of the mitochondria.

Abstract: To establish whether the prophylactic use of verapamil, nifedipine or propranolol protects heart muscle against the deleterious effects of global ischemia and reperfusion, rabbits were injected subcutaneously twice daily with 2.0 mg/kg of one of these drugs for 4 to 5 days. The hearts were then isolated, paced and either perfused aerobically, made totally ischemic for 90 minutes or made ischemic for 90 minutes and then reperfused. At the end of this time some of the hearts were assayed for adenosine triphosphate (ATP), creatine phosphate (CP) and calcium (Ca ++ ). Other hearts were homogenized, the mitochondria harvested and monitored for oxidative phosphorylating and ATP-generating capacity and Ca ++ content. The effect of Ca ++ on the ATP-generatlng capacity of cardiac mitochondria was also determined. Hearts that were made ischemic gained Ca ++ . The endogenous stores of ATP and CP were depleted; the mitochondria accumulated Ca ++ and the oxidative phosphorylating activity (respiratory control index and oxygen quotient) was impaired. During reperfusion, tissue and mitochondrial Ca ++ was substantially increased, the capacity of the mitochondria to use O 2 for state III respiration was further impaired and the ATP-generating capacity reduced. Resting tension increased and there was only a small recovery of active tension generation. Hearts from the rabbits treated with propranolol, verapamil or nifedipine were protected against ischemia, and ischemia with reperfusion-induced decline in the ATP-generating and O 2 -utillzing capacity of the mitochondria. There was also a less marked increase in tissue and mitochondrial Ca ++ and the systolic tension-generating capacity of the hearts was better maintained.