Effects of ischemia on rat myocardial function and metabolism in diabetes.

Abstract

The function and metabolism of hearts removed from diabetic rats and subsequently . perfused in vitro were investigated. Diabetic hearts perfused under aerobic conditions had higher tissue levels of total CoA and long-chain acyl-CoA, lower levels of total camitine, but higher levels of long-chain acyl camitine esters, and used glucose at slower rates than did normal hearts. At low levels of cardiac work, mechanical function of the diabetic hearts was not significantly different than normal hearts for perfusion periods of up to 65 minutes. A mild form of whole heart ischemia (i.e., a 50% reduction in coronary flow) was tolerated just as well by hearts from diabetic rats as by those from normal rats. This degree of ischemia accelerated glucose use in normal but not in diabetic hearts. Mild ischemia resulted in increased tissue levels of acyl esters of CoA and camitine in both normal and diabetic hearts, but the rise was greater in the diabetic tissue. A more severe form of ischemia resulted in a faster rate of ventricular failure in hearts from both normal and diabetic rats, but the rate of failure was fastest in the diabetic hearts. This earlier mechanical failure in diabetic tissue was associated with a more rapid rise in tissue long-chain acyl-CoA and acyl camitine esters. Tissue K + was lost during ischemic perfusion to about the same extent in both normal and diabetic hearts. Thus, early pump failure of diabetic hearts in response to ischemia was not associated with a greater loss of cellular