title: Postconditioning: a mechanical maneuver that triggers biological and molecular cardioprotective responses to reperfusion.
abstract: Infarct size is determined not only by the duration and severity of ischemia, but also by pathological processes initiated at reperfusion (reperfusion injury). Numerous pharmacological strategies have been reported which administer drugs at or just before the onset of reperfusion, with subsequent salubrious effects, notably a reduction in infarct size. However, few if any of these strategies have become standard of care in the catheterization laboratory setting. Postconditioning, defined as repeated brief cycles of reperfusion interrupted by ischemia (or hypoxia) applied at the onset of reperfusion, was recently introduced as a mechanical strategy to attenuate reperfusion injury. Postconditioning intervenes only during the first few minutes of reperfusion. However, it reduces endothelial activation and dysfunction, the inflammatory response to reperfusion, necrosis, and apoptosis both acutely and long-term. Cardioprotection has been demonstrated by multiple independent laboratories and in multiple species. Postconditioning stimulates G-protein coupled receptors by their cognate endogenously released ligands and surprisingly activates survival kinases that may converge on mitochondrial K(ATP) channels and the permeability transition pore. Postconditioning has been shown in two clinical studies to reduce infarct size in patients undergoing percutaneous coronary intervention in the catheterization laboratory, and at least five other studies are in some phase of implementation. This significant reduction in infarct size has implications for reduction in heart failure as a consequence of myocardial infarction, but this link has yet to be demonstrated. The salubrious effects of postconditioning are an indirect validation of the experimental and clinical importance of reperfusion injury in the setting of coronary artery occlusion.
authors.affiliation: Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory Crawford Long Hospital, 550 Peachtree Street NE, Atlanta, GA 30308-2225, USA. jvinten@emory.edu
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D004727:Endothelium / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D019157:Ischemic Preconditioning, Myocardial; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium; D011493:Protein Kinase C; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011493:Protein Kinase C