Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fattyrats

We measured infarct size after coronary occlusion (30 min) and reperfusion (24 h) in genetic non-insulin-dependent Zucker diabetic fatty (ZDF) rats wi th and without 4-wk cholesterol feeding. Infarct size was similar in ZDF ra ts and lean control rats but was significantly larger in cholesterol-fed di abetic rats than in cholesterol-fed lean rats (P < 0.05). Plasma levels of glucose, insulin, and triglycerides were significantly higher in diabetic r ats and were not influenced by cholesterol feeding. The increase in total p lasma cholesterol induced by cholesterol feeding was significantly greater in diabetic rats than in lean rats (P < 0.05). A significant positive corre lation was found between total plasma cholesterol and infarct size (P < 0.0 5). Myeloperoxidase activity, as an index of neutrophil accumulation, was s ignificantly higher and expression of P-selectin was more marked in the isc hemic myocardium of cholesterol-fed diabetic rats than of cholesterol-fed l ean rats. Acetylcholine-induced endothelium-dependent relaxation (EDR) of a ortic rings was markedly impaired in cholesterol-fed diabetic rats. Thus ch olesterol feeding significantly exacerbated myocardial injury produced by c oronary occlusion-reperfusion in non-insulin-dependent diabetic rats, possi bly because of enhanced expression of P-selectin and impairment of EDR in t he coronary bed.