Diabetic patients are more prone to develop postinfarction complications. It remained unclear whether diabetes mellitus- or sulfonylureas-associated changes of ATP-sensitive potassium (K(ATP)) channels, an integral player in ischemic preconditioning, are responsible for the increased mortality. The purpose of this study was to determine the impact of diabetes mellitus per se and different sulfonylurea administration on cardioprotective effects in diabetic patients undergoing coronary angioplasty. Myocardial ischemia after coronary angioplasty was evaluated in 20 nondiabetic and 23 diabetic patients chronically taking either glibenclamide or glimepiride. Nondiabetic patients treated with glimepiride significantly lowered the ischemic burden assessed by an ST-segment shift, chest pain score, and myocardial lactate extraction ratios compared with the glibenclamide-treated patients, implying that acute administration of glimepiride did not abolish cardioprotection. In the diabetic glibenclamide-treated group, the reduction in the ST-segment shift afforded by nicorandil in the first inflation (-58% vs. the first inflation in the glibenclamide group alone) was similar to that afforded by preconditioning (-59% during the second vs. the first inflation). In glimepiride-treated groups, the magnitude of attenuated lactate production was less in diabetes than that in nondiabetes at the second inflation, suggesting that diabetes mellitus per se plays a role in determining lactate production. Our results show that both diabetes mellitus and sulfonylureas can act in synergism to inhibit activation of K(ATP) channels in patients undergoing coronary angioplasty. The degree of inhibition assessed by metabolic and electrocardiographic parameters is less severe during treatment with glimepiride than with glibenclamide. Restitution of a preconditioning response in glimepiride-treated patients may be the potential beneficial mechanism.

Background-The ischemic preconditioning response among elderly patients is known to be lower than in adult patients.Since mitochondrial ATP-sensitive potassium (K ATP ) channels exert preconditioning effects, we undertook this study to determine whether this attenuated activation of K ATP channels influences the reduced responsiveness of elderly patients to ischemic preconditioning. Methods and Results-Fifty-six patients undergoing angioplasty for a major epicardial coronary artery were randomly allocated to either an ischemic preconditioning group, a nicorandil (an agonist of K ATP channels) group, or a glibenclamide (an antagonist of K ATP channels), group based on their age: adult groups (nϭ26; age, Յ55 years; mean age, 45Ϯ5 years) and elderly groups (nϭ30; age, Ն65 years; mean age, 71Ϯ3 years). Ischemic preconditioning with a 120-second coronary occlusion significantly lowered the ischemic burden assessed by ST-segment shift, chest pain score, and myocardial lactate extraction ratios in the adult group. This did not occur in the elderly group. The impaired preconditioning responsiveness in the elderly patients was reversed by nicorandil administration or an ischemic period lengthened to 180 seconds. However, nicorandil-induced cardioprotection was abolished by administering glibenclamide in both the adult and elderly groups. Conclusions-The present study demonstrates that preconditioning significantly enhances the tolerance of the heart to subsequent ischemia in adults but not in senescent patients. Since prolonged ischemia and nicorandil are able to mimic preconditioning and can reverse impaired responsiveness, impaired preconditioning of the aged heart appears to be due to an attenuated activation of K ATP channels.