Impairment of myocardial protection in type 2 diabetic patients.
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.
Lee
Tsung-Ming
TM
National Taiwan University College of Medicine, Department of Internal Medicine, Cardiology Section, National Taiwan University Hospital, Taipei, Taiwan 10002. tsungm.lee@msa.hinet.net
Chou
Tsai-Fwu
TF
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001794:Blood Pressure; D002637:Chest Pain / Q000139:chemically induced / Q000175:diagnosis / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004562:Electrocardiography; D005260:Female; D005905:Glyburide / Q000008:administration & dosage; D006339:Heart Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D019194:Ischemic Preconditioning; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000175:diagnosis* / Q000628:therapy; D020108:Nicorandil / Q000008:administration & dosage; D015221:Potassium Channels / Q000819:agonists; D011446:Prospective Studies; D013453:Sulfonylurea Compounds / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D020108:Nicorandil; D019344:Lactic Acid; C057619:glimepiride; D005905:Glyburide