KETAMINE-XYLAZINE ANESTHESIA PERMITS A K-ATP CHANNEL ANTAGONIST TO ATTENUATE PRECONDITIONING IN RABBIT MYOCARDIUM

Objective: ATP sensitive potassium (K-ATP) channels have been implicat ed in the mechanism of ischaemic preconditioning, though apparently no t in the pentobarbitone anaesthetised rabbit model. The aim of this st udy was to test whether potassium channel activation and blockade woul d alter protection in ketamine-xylazine anaesthetised rabbits. Methods : In situ rabbit hearts (n = 50) received 30 min regional ischaemia an d 3 h reperfusion. Some hearts were preconditioned by 5 min regional i schaemia and 10 min reperfusion prior to the long ischaemia. Infarct s ize was determined by tetrazolium staining. Results: In rabbits anaest hetised with ketamine-xylazine, brief preconditioning ischaemia contin ued to produce much smaller infarcts than in nonpreconditioned animals [19(SEM 2)% v 47(3)%, p less than or equal to 0.05]. Blocking K-ATP c hannels by pretreating with glibenclamide resulted in 35(3)% infarctio n in non-preconditioned hearts and aborted protection in preconditione d hearts [35(4)% infarction]. Substituting the potassium channel activ ator pinacidil for the short ischaemia caused comparable reductions in infarct size [28(4)%, p less than or equal to 0.05 v non-precondition ed hearts]. This protection, however, could be blocked by concomitant administration of the adenosine receptor blocker 8-(p-sulphophenyl)the ophylline (SPT) [44(3)% infarction]. Conclusions: When ketamine-xylazi ne anaesthesia was employed, the protective effects of ischaemic preco nditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischaemic preconditioning. Bec ause the protection afforded by pinacidil could be blocked by SPT, how ever, there is still some question whether the K-ATP channel is the en d effector of preconditioning.