Studies of Ischemic Preconditioning Mechanisms in Langendorff Rat Heart Model the Impact of Phosphocreatin Kinase and ATP Sensitive Potasium Channels Pharmachological Openers and Blockers on Cardioprotection

Ischemic preconditioning (IPC) induced by administration of brief episodes of ischemia-reperfusion represents a protective mechanism of the heart against prolonged episodes of ischemia. Although the mechanism of ischemic preconditioning has been extensively studied, however, until now it is insufficient elucidated. Using a Langendorff rat heart model with 45 minutes ischemia followed by 120 minute reperfusion we aimed to evaluate the role of Phosphocreatin Kinase-C (PCK) in ischemic rat myocardium and demonstration of its involvment in the path of pharmachological preconditioning (PP) by using PKC activators 1,2-dioctanoyl-sn-glycerol (DOG) and inhibitors chelerythrine (CHE) and evaluation of the role of KATP channels in pharmachological preconditioning (PP) mechanism by administration of a KATP channel opener (Cromakalim) (CRK) or by blocking the opening of KATP channels with glibenclamide(GLB). The activators of PCK(DOG) and of K ATP channel (CRK) limited the infarct size when perfused before lethal ischemia, mimicking the ischemic preconditioning in rat heart When activator of PCK DOG + GLB, a KATP channel inhibitor were coperfused before the lethal ischemia, there was an increase in myocardial infarct size, expressed as a percentage of the area at risk, versus control, the cardioprotective effect of DOG being abolished by GLB. The same results were obtained when CHE the inhibitor of PCK was coperfused with CRK the activator of K ATP channel. The effect of CHE and GLB perfused at the beginning of IPC resulted in loss of protection accompanied by a significant increase in infarct size area. The finding that treatment with a DOG PKC activator and CRK activator of K ATP channel gives a similar degree of protection against infarction as that seen after ischemic preconditioning and that this protection can be blocked by CHE a PCK pharmachological inhibitor provides support for the hypothesis that PKC plays a pivotal role in ischemic preconditioning. Our data may have a significance in pharmachological preconditioning (PP) with decrease in infarct size as an end point.