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 latter 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 glibenclamide affects infarct size by modulating interstitial adenosine levels, Interstitial adenosine and total purine concentrations were assessed in open-chest rabbits by the microdialysis technique, Dialysis fibers were inserted into myocardium served by a coronary artery branch surrounded 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 animals also received glibenclamide, The control levels of adenosine in the dialysate were comparable in the three groups, as were: those of total purines, and the infusion of glibenclamide caused no change. Ischemia led to 10- to 20-fold increases in interstitial adenosine and 10- to 40-fold rises in total purine concentrations, These increases were equivalent in all groups, Furthermore, infarct size as a percentage of the myocardium at risk was also comparable in the three groups. Neither the anesthetic agent nor glibenclamide appears to modulate interstitial adenosine release from ischemic tissue.