An Experiment Study On The Effect Of Sulfonylureas On Myocardial Ischemic Preconditioning In Rabbits

OBJECTIVEIn order to know if sulfonylureas have adverse effects on the cardiolvascular system, we took healthy Newsland white rabbits and observed the effects of glibenclamide, glimepiride and glipizide on the protection from myocardial ischemic preconditioning(IPC).METHODThe heathy Newsland white rabbits were divided into nine groups randomly, native group, control group, IPC group, glibenclamide group, glibenclamide＋IPC group, glimepiride group, glimepiride＋IPC group, glipizide group, glipizide＋IPC group. A thoracotomy was performed to copy IPC and ischemic/reperfusion models. Tightening left anterior descendening of the coronary artery produced regional ischemia and releasing allowed reperfusion. During the experiments, ECG of limb leads and blood samples were recorded. After the experiments, the sizes of myocardial infarction were calculated and the specimen were observed through light microscope and electron microscope.RESULTThere were no differences in body weight, cardiac weight, baseline glucose baseline insulin and baseline troponin T in all groups.There was a significent increase in glucose and a significent decrease in insulin from the baseline in native group, control group, and IPC group, and there were adverse changes in the rest groups.Apart from native group, there were a significent increase in troponin T from the baseline in all the groups, troponin T was higher in glibenclamide＋IPC group than IPC group, while there were no differences in glimepiride＋IPC group, glipizide＋IPC group and IPC group.The sizes of myocardial infarction were higher in glibenclamide＋IPC group than IPC group, while there were no differences in glimepiride＋IPC group, glipizide＋IPC group and IPC group.Light microscopical examination: myocardial nucleus extinction, eosin staining darker, lots of nucleus fragments of necrotizing inflammatory cells.Electron microscopical examination: broadened I bands, clouding Z lines, swollen mitochondria and chromatin condensation in the nucleus.CONCLUSIONS1.We can establish stable animal myocardial IPC models by a thoracotomy.2.IPC is a powerful endogenous myocardial protection mechenism. It can reduce sizes of myocardial infarction and decrease troponin T.3.Glibenclamide abolishes the protection of IPC.4.Glimepiride and glipizide have no effects on IPC.