Cardioprotection of ischemic postconditioning and pharmacological post-treatment with adenosine or acetylcholine.

The recent discovery of ischemic postconditioning is a landmark of anti-reperfusion injury. The medical community has a preference for postconditioning because it is easier to control in clinic and has reliable benefits to heart compared with preconditioning. Postconditioning is defined as a series of brief mechanical interruptions of blood flow applied at the very onset of reperfusion. It can reduce irreversible post-ischemic injury and protect myocardium. There are two important factors in the algorithm of postconditioning: cycle number and duration of intermittent episodes. The latter may depend on species and is more important than cycle number. Postconditioning-induced infarct-sparing effect persists not only after the acute phase of reperfusion but also after a prolonged reperfusion. However, whether cardioprotection of postconditioning is related to preservation of endothelial function and attenuation of oxidative damage is still under debate. Up-regulating the reperfusion injury salvage kinase (RISK) pathway is one of the most important mechanisms in cardioprotection of postconditioning, including activation of phosphatidylinositol 3-kinase (PI3K)-Akt and/or extracellular signal-regulated kinase (ERK), which reduces apoptosis and necrosis by inhibiting the opening of mitochondrial permeability transition pore (mPTP). But the signal transduction of these two pathways needs further research. In order to be more suitable for clinical application, researchers translate mechanical maneuver into drug intervention to investigate whether drug can simulate ischemic postconditioning in cardioprotection, termed pharmacological postconditioning. Adenosine is one of the most extensive and prospective drugs in pharmacological postconditioning study. However, in our laboratory we demonstrate that acetylcholine is able to induce pharmacological postconditoning through mitochondrial ATP-sensitive potassium channel. The present article reviews the protective effects and signal transduction of postconditioning, especially the mechanisms and clinical application of adenosine- and acetylcholine-induced pharmacological postconditioning.