BLOCKADE OF THE K-ATP-CHANNEL BY GLIBENCLAMIDE AGGRAVATES ISCHEMIC-INJURY, AND COUNTERACTS ISCHEMIC PRECONDITIONING

Blocking of the K-ATP-channel with glibenclamide has been shown to abo lish the infarct-reducing effect of ischemic preconditioning in dog an d swine. In the rabbit the results have been divergent purportedly rel ated to anaesthesia. The aim of this study was to investigate the impo rtance of the K-ATP-channel in a rabbit model where anaesthesia was no t a confounding factor. Isolated rabbit hearts perfused with a Krebs-H enseleit bicarbonate buffer were subjected to 30 min regional ischemia by ligating a coronary artery, followed by 120 min reperfusion. The p reconditioning protocol was 5 min global ischemia and 10 min reperfusi on. Glibenclamide (100 mu m) was added to the perfusion solution befor e the preconditioning ischemia and stopped after 5 min regional ischem ia. Infarcts were measured with tetrazolium staining and risk zones wi th fluorescent microspheres. The main results expressed as percent inf arction of the risk zone +/- SEM for the different groups are as follo ws: control (n = 12) 26.8 +/- 3.2, ischemic preconditioning (IF) (n = 9) 7.3 +/- 1.5, (p < 0.05 vs. control), control +/- glibenclamide (n = 9) 46.9 +/- 7.3 (p < 0.05 vs. control), IP + glibenclamide (n = 10) 3 8.3 +/- 6.9 (p < 0.05 vs. IF). These results show that glibenclamide t reatment aggravates ischemia. Also, under the influence of glibenclami de ischemic preconditioning was no longer effective in reducing infarc t size in the isolated perfused rabbit heart.