EFFECTS OF ANESTHESIA AND K+ ATP CHANNEL BLOCKADE ON INTERSTITIAL ADENOSINE ACCUMULATION IN ISCHEMIC RABBIT MYOCARDIUM

Glibenclamide, a K-ATP(+) channel antagonist, blocks the anti-infarct effect of ischemic preconditioning in rabbits, but only when the latte r are anesthetized with ketamine-xylazine. Furthermore, the protection triggered by pinacidil, a K-ATP(+) channel opener, can be aborted by treatment with the adenosine antagonist 8-(P-sulfophenyl)theophylline. This study tests whether either the anesthetic regimen or glibenclami de affects infarct size by modulating interstitial adenosine levels, I nterstitial adenosine and total purine concentrations were assessed in open-chest rabbits by the microdialysis technique, Dialysis fibers we re inserted into myocardium served by a coronary artery branch surroun ded by a snare. All animals sustained a 30-min coronary occlusion and then 120-min reperfusion, Rabbits were anesthetized with either sodium pentobarbital or a ketamine-xylazine mixture, Half of the latter anim als also received glibenclamide, The control levels of adenosine in th e dialysate were comparable in the three groups, as were: those of tot al purines, and the infusion of glibenclamide caused no change. Ischem ia led to 10- to 20-fold increases in interstitial adenosine and 10- t o 40-fold rises in total purine concentrations, These increases were e quivalent in all groups, Furthermore, infarct size as a percentage of the myocardium at risk was also comparable in the three groups. Neithe r the anesthetic agent nor glibenclamide appears to modulate interstit ial adenosine release from ischemic tissue.