MYOCARDIAL ENERGY-METABOLISM AND CONTRACTILITY IN RABBITS WITH DIABETIC CARDIOMYOPATHY - EFFECTS OF ISCHEMIA AND REPERFUSION

Hemodynamic parameters, mitochondrial respiratory rate, the contents of high-energy phosphates (ATP, ADP, AMP, and phosphocreatine), and creatine phosphokinase (CPK)* activity were studied in isolated perfused hearts (Langendorff preparations) of normal and diabetic rabbits before ischemia, after a 40-min period of total ischemia, and upon reperfusion. Compared to normal hearts, the diabetic hearts displayed reduced rates of contraction (+dP/dt) and relaxation (-dP/dt) and lower heart rate and cardiac performance. Saponin-treated fibers from diabetic hearts had lower mitochondrial respiratory rates and significantly reduced contents of A TP and ADP with intact phosphocreatine and total creatine levels. Total CPK activity and that of its mitochondrial isoenzyme in diabetic myocardium were significantly lower than normal levels. After ischemia, the diabetic hearts recovered their mechanical performance to a greater extent than the normal controls. In addition, concentrations of ATP were higher and restored more rapidly on reperfusion in diabetic than in normal myocardium. The data suggest that, although contractility and energy metabolism are somewhat impaired in diabetic hearts, they are more resistant to ischemia and reperfusion.