title: Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning.
abstract: Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning). The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date.
authors: From the Institute for Pathophysiology, West German Heart and Vascular Centre, University of Essen Medical School, Essen, Germany. gerd.heusch@uk-essen.de.
authors: Gerd
authors: G
authors: Heusch
mesh_terms: D000818:Animals; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome
keywords: acute myocardial infarction; ischemic postconditioning; ischemic preconditioning; myocardial ischemia; reperfusion