title: Postconditioning and protection from reperfusion injury: where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology.
abstract: Ischaemic postconditioning (brief periods of ischaemia alternating with brief periods of reflow applied at the onset of reperfusion following sustained ischaemia) effectively reduces myocardial infarct size in all species tested so far, including humans. Ischaemic postconditioning is a simple and safe manoeuvre, but because reperfusion injury is initiated within minutes of reflow, postconditioning must be applied at the onset of reperfusion. The mechanisms of protection by postconditioning include: formation and release of several autacoids and cytokines; maintained acidosis during early reperfusion; activation of protein kinases; preservation of mitochondrial function, most strikingly the attenuation of opening of the mitochondrial permeability transition pore (MPTP). Exogenous recruitment of some of the identified signalling steps can induce cardioprotection when applied at the time of reperfusion in animal experiments, but more recently cardioprotection was also observed in a proof-of-concept clinical trial. Indeed, studies in patients with an acute myocardial infarction showed a reduction of infarct size and improved left ventricular function when they underwent ischaemic postconditioning or pharmacological inhibition of MPTP opening during interventional reperfusion. Further animal studies and large-scale human studies are needed to determine whether patients with different co-morbidities and co-medications respond equally to protection by postconditioning. Also, our understanding of the underlying mechanisms must be improved to develop new therapeutic strategies to be applied at reperfusion with the ultimate aim of limiting the burden of ischaemic heart disease and potentially providing protection for other organs at risk of reperfusion injury, such as brain and kidney.
authors.affiliation: Service d'Explorations Fonctionnelles Cardiovasculaires and Inserm U886, Hospices Civils de Lyon, University of Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
authors.forename: Gary F
authors.initials: GF
authors.lastname: Baxter
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
authors.forename: Derek M
authors.initials: DM
authors.lastname: Yellon
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000465:Algorithms; D000818:Animals; D002309:Cardiology; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D005060:Europe; D019317:Evidence-Based Medicine; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects / Q000379:methods; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D012955:Societies, Medical; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents