Comparison of the efficacy of glibenclamide and glimepiride in reperfusion-induced arrhythmias in rats

The effect of glibenclamide and glimepiride, two orally active antidiabetic sulphonylurea derivatives, was investigated on the development of reperfus ion-induced arrhythmias and it was compared to their blood glucose lowering action. Arrhythmias were produced by reperfusion following 6 min coronary artery ligation in anaesthetised rats. Glimepiride pretreatment (0.001-0.01 -0.1-5.0 mg/kg i.p., 30 min before coronary occlusion) significantly decrea sed the incidence of irreversible ventricular fibrillation and increased th e survival rate during reperfusion (64%, 61%, 60%, and 67% vs. 27% in contr ols). Glibenclamide produced similar effect (81% survival) only in a dose o f 5 mg/kg, while smaller doses were ineffective. The minimal hypoglycaemic dose and the dose required to inhibit significantly the oral glucose loadin g-induced hyperglycaemia were similar (1 and 0.1 mg/kg, respectively) after glibenclamide and glimepiride. It is concluded that although the blood glu cose lowering potency of glibenclamide and glimepiride is rather similar, g limepiride appears to be more potent than glibenclamide in preventing reper fusion-induced cardiac arrhythmias. (C) 1999 Elsevier Science B.V. All righ ts reserved.