PT  - JOURNAL ARTICLE
AU  - G J Grover
AU  - S Dzwonczyk
AU  - P G Sleph
AU  - C A Sargent
TI  - The ATP-sensitive potassium channel blocker glibenclamide (glyburide) does not abolish preconditioning in isolated ischemic rat hearts.
DP  - 1993 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 559--564
VI  - 265
IP  - 2
4099  - http://jpet.aspetjournals.org/content/265/2/559.short
4100  - http://jpet.aspetjournals.org/content/265/2/559.full
SO  - J Pharmacol Exp Ther1993 May 01; 265
AB  - Previous studies have indicated that the ATP-sensitive potassium channels blocker glibenclamide (glyburide) can abolish preconditioning in canine models of myocardial ischemia. Recently, an isolated rat heart model of preconditioning has been developed that may be ideal for studying the mechanisms of preconditioning. In the present study, we determined the effect of glyburide on preconditioning in isolated rat hearts. Rat hearts were isolated and retrogradely perfused with oxygenated Krebs'-Henseleit solution. They were then subjected to four periods of total global ischemia of 5-min duration, separated by 5-min reperfusion. The hearts were then subjected to 30-min global ischemia followed by 30-min reperfusion and contractile function and lactate dehydrogenase release determined. Non-preconditioned hearts sustained severe damage. Glyburide (1-100 microM) 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 reperfusion lactate dehydrogenase release and reperfusion end diastolic pressure (contracture). Glyburide had modest preischemic cardiodepressant and vasoconstrictor effects at 1-30 microM, whereas 100 microM caused a 50% reduction in preischemic coronary flow. Despite these effects, none of these concentrations of glyburide affected the efficacy of preconditioning. These studies indicate that preconditioning in isolated rat hearts does not occur via a glyburide- (and thus presumably ATP-sensitive potassium channel) sensitive mechanism.