Modulation of cardiac interstitial noradrenaline levels through KATP channels during ischemic preconditioning in rabbits:: comparison of the effect of anesthesia between pentobarbital and ketamine plus xylazine

In rabbits, both the stimulation of alpha 1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. One candidate for the mechanism of PC is noradrenaline (NA), which stimulates alpha 1-adrenoceptors in the myocardium during PC. Opening of the K-ATP channel is considered to be another candidate for PC, since a K-ATP channel blocker, glibenclamide, blocks the infarct size-reducing effect of the PC of 5-min ischemia and 5-min reperfusion in rabbits anesthetized with ketamine + xylazine. However, in rabbits anesthetized with pentobarbital, the infarct size-reducing effect of PC was not blocked by glibenclamide. The effect of glibenclamide on the PC effect thus differs depending on the anesthesia used. Therefore, we speculated that the increase in cardiac interstitial NA levels induced by PC may be modified by the anesthesia used, thus regulating the effect of glibenclamide on the PC effect. In open-chest Japanese white male rabbits anesthetized with pentobarbilal or ketamine + xylazine, myocardial interstitial NA levels were measured before and during the PC of 5-min ischemia and 5min reperfusion in the presence or absence of the K-ATP channel blocker, glibenclamide (0.3 mg/kg, i.v.), using a microdialysis technique. The NA levels were measured using high-performance liquid chromatography coupled with electrochemical detection. The PC of 5-min ischemia and 5-min reperfusion significantly elevated the interstitial NA level. This increase in the NA level was not blocked by glibenclamide under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, the PC did not cause an increase in the myocardial interstitial NA level in either the absence or the presence of glibenclamide. In conclusion, PC elevates the myocardial interstitial NA level, and this elevation is not mediated through the opening of the K-ATP channel under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, PC does not cause an increase in the myocardial interstitial NA level. This may explain the discrepancy in the blocking effect of glibenclamide on the infarct size-reducing effect of PC between anesthesia with pentobarbital and ketamine + xylazine.