Reversibility of diabetic cardiomyopathy with insulin in rabbits

Diabetes mellitus causes a cardiomyopathy in human subjects, independent of atherosclerotic coronary artery disease. Ventricular papillary muscle function studies in chronically diabetic rats and rabbits have shown diminished contractility and a prolonged duration of contraction. In rats there was complete reversibility of these changes with insulin therapy. However, the effects of insulin on the myocardial mechanics of diabetic rabbits have not been studied. Therefore, rabbits diabetic for 3-4 mo (after alloxan injection) were treated with PZI insulin for 3-4 mo, and the mechanical performance of their right ventricular papillary muscles was compared with that of untreated diabetic animals and age-matched controls. Insulin therapy normalized serum glucose concentration. All abnormalities in papillary muscle function were completely reversed in insulin-treated animals. Norepinephrine (NE) dose responses were also evaluated in muscles from all groups. There were no differences in the positive inotropic effects of NE between groups. However, the data suggested, in diabetic animals a blunted response of peak relaxation rate to NE; this abnormality was reversed in muscles from treated animals. These findings indicate that previous work on diabetic rats can be extended to diabetic rabbits and suggest that chronic insulin therapy completely reverses the contractile alterations in hearts from these diabetic animals.