THE ATP-SENSITIVE POTASSIUM CHANNEL BLOCKER GLIBENCLAMIDE (GLYBURIDE)DOES NOT ABOLISH PRECONDITIONING IN ISOLATED ISCHEMIC RAT HEARTS

Previous studies have indicated that the ATP-sensitive potassium chann els blocker glibenclamide (glyburide) can abolish preconditioning in c anine models of myocardial ischemia. Recently, an isolated rat heart m odel of preconditioning has been developed that may be ideal for study ing the mechanisms of preconditioning. In the present study, we determ ined the effect of glyburide on preconditioning in isolated rat hearts . Rat hearts were isolated and retrogradely perfused with oxygenated K rebs'-Henseleit solution. They were then subjected to four periods of total global ischemia of 5-min duration, separated by 5-min reperfusio n. The hearts were then subjected to 30-min global ischemia followed b y 30-min reperfusion and contractile function and lactate dehydrogenas e release determined. Non-preconditioned hearts sustained severe damag e. Glyburide (1-100 muM) pretreatment had no effect on the severity of 30-min global ischemia and 30-min reperfusion. Preconditioning caused significant improvements in reperfusion contractile function (25-fold increase in left ventricular developed pressure) and reductions in re perfusion lactate dehydrogenase release and reperfusion end diastolic pressure (contracture). Glyburide had modest preischemic cardiodepress ant and vasoconstrictor effects at 1-30 muM, whereas 100 muM caused a 50% reduction in preischemic coronary flow. Despite these effects, non e of these concentrations of glyburide affected the efficacy of precon ditioning. These studies indicate that preconditioning in isolated rat hearts does not occur via a glyburide- (and thus presumably ATP-sensi tive potassium channel) sensitive mechanism.