Oral hypoglycemic sulfonylurea glimepiride preserves the myoprotective effects of ischemic preconditioning

Background. To investigate whether the sulfonylurea glimepiride affects the myoprotective effects of ischemic preconditioning (IPC), isolated rabbit hearts were perfused with Krebs-Henseleit solution. Methods. Eight hearts underwent IPC consisting of two cycles of 5 min global ischemia and reperfusion. Six hearts received a 5-min infusion of 10 muM glimepiride, six hearts received a 5-min infusion of 50 muM glimepiride, and seven hearts received a 5-min infusion of 10 muM glibenclamide before IPC. Seven hearts received a 5-min infusion of the selective mitochondrial K-ATP channel opener diazoxide (50 muM). Other hearts received a 5-min infusion of 10 muM glimepiride (n = 6), 50 muM glimepiride (n = 6), or 10 muM glibenclamide (n = 7) before diazoxide. Seven hearts served as a control. All groups then were subjected to 1 h of regional ischemia, followed by I h of reperfusion. LV pressures, monophasic action potential duration (APD(50)), and infarct size were measured. Results. Both IPC and diazoxide significantly prolonged APD(50) and preserved diastolic function at 60 min of reperfusion compared to control. In addition, both groups reduced infarct size compared to control. Glibenclamide, but not glimepiride reversed these effects. Conclusion. Glimepiride offers less cardiovascular effects than glibenclamide, possibly due to its lower affinity for the mitochondrial K-ATP channels. (C) 2002 Elsevier Science (USA).