Preconditioning and Postconditioning

Ischemia-reperfusion injury (IRI) induced myocardial damage is responsible 50% for the size of the final infact, thereby affording a promising cardioprotective target. These cardioprotective phenomenons are ischemic preconditioning (PC) and postconditioning (PostC). Summarily, the cardioprotective effect caused by the short periods of sublethal ischemia detached by short phases of reperfusion, which able to render the heart resistant to infarction from a prolonged, subsequent lethal episode of ischemia. Preconditioning is one of the most powerful cardioprotective intervention, to dimish the ischemia-reperfusion caused heart damage. The beneficial roles of ischemic preconditioning, first reported by Murry et al. in 1986. They proved that animal group which got four-time 5 minute coronary occlusion/5 minute reperfusion, as preconditioning and after a 40 min sustained circumflex occlusion, suffered only one-quarter as much necrosis as without preconditioning. Hausenloy et al. found that preconditioning cause cardioprotection at reperfusion. It is demonstrated that ischemic preconditioning include two phases: an early preonditioning, which starts at the ischemic phase and lasts for 2-3 hours, and late preconditioning, this phase is mainfests at 24 hours and lasts until 72-96 hours after initial ischemia. Remote preconditioning is suggested by Przyklenk et al. This is a non invasive form of the administration of preconditioning. Birnbaum et al. found that briefly limiting the blood flow on the lower limb pacing the leg muscle, thus preconditioning able to reduce myocardial infarct size. Oxman et al. demonstrated a less invasive method, inducing in the hind-limb, for ten minutes by tourniquet able to reduce sustained ischemic insult caused myocardial damage.

Zhao et al. proved in canine model, that three short (30s) periods of reperfusion/occlusion directly after the initial reperfusion were nearly as protective as ischemic preconditioning, and reduced the infarct size and enothelial dysfunction. This manuver is called ischemic postconditioning. Agreement with that, Kin et al. demonstrated the same cardioprotective effect by postconditioning in three cycles on the first minute of reperfusion in rat myocardial ischemia-reperfusion model, and proved that postconditioning also protective in rat heart. Ischemic pre- and postconditioning are members of the group of mechanical conditioning. In the procedure of conditioning, there are other methods, such as pharmacological and heat stress induced conditioning, which are seems to be as protective as mechanical ischemic conditioning.

Several studies found that the beneficient aspects of preconditioning and postconditioning can also induced by pharmacological substances, such as adenosine, urocortin, volatile and isoflurane. Adenosine is a metabolite of adenine nucleotids. Liu et al. found that infusion intracoronally for 5 minutes of adenosine and then recovery for 10 minutes seems to as protective as preconditioning in rabbit heart. Yao et al. proved that adenosine administration to dog heart able to duplicate the beneficial effect of ischemic preconditioning. They applied the adenosine by intracoronal infusion for 10 minutes, then 10 minutes of recovery. After that they onserved a reduced infarct size in dog hearts. Furthermore, rendering 8-SPT, an adenosine antagonist, is supresses the protection in ischemic preconditioned heart. The corticotropin releasing factor (CRF) family member, urocortin, is a 41 amino acid peptide, which expressed in both human and rat heart. Urocortin has been demonstrated to protect rat cardiomyocytes from apoptosis, when administrated in hypoxia or the pahse of the reperfusion. Cserepes et al. found that preconditioning induced by urocortin is as protective as caused by adenosine, and they proved that postconditioning by urocortin is seems to much more protective than ischemic postconditioning alone. It is suggested that volatile anesthetics are able to induce cardioprotective effects. This mechanism is proceeds by activation of PKC, K_ATP channel, ROS and cyclooxygenase-2. Evidences showed that administration of volatile, in supraclinical concentration is led to a higher cardioprotective event, than applied a lower concentration. Zaugg et al. showed that volatile induced cardioprotection is mediated by mitochorial K_ATP channel, through an activation by protein kinase C. It is well established that anesthetics, like halothane or isoflurane are able to change mitochondrial function, via inhibit the electron transport chain in the level of complex I (NADH ubiquinone oxidoreductase), and thus this is cause a decreased production of ROS. Isoflurane is cause depolarization in mitochondrial membrane, which is seems to responsible for the cardioprotective effect of isoflurane-induced preconditioning. Another method is heat shock (HS) induced preconditioning, which has the beneficial, that its non-pharmacological. Cells in stress conditions, are able to tolerate higher oxidative stress, because of the accumulation of heat-shock proteins. Currie et al. found in isolated rat heart, that HS induced preconditioning is improved the contractile recory at the time of reperfusion. The molecular mechanism behind HS induced preconditioning is not fully known, it is suggested involvement of MAPKs, ROS, K_ATP channels, PKCs, opioids and heat-shock proteins, such as Hsp70 and Hsp90.