title: Reperfusion injury as a therapeutic challenge in patients with acute myocardial infarction.
abstract: Cardiomyocyte death secondary to transient ischemia occurs mainly during the first minutes of reperfusion, in the form of contraction band necrosis involving sarcolemmal rupture. Cardiomyocyte hypercontracture caused by re-energisation and pH recovery in the presence of impaired cytosolic Ca(2+) control as well as calpain-mediated cytoskeletal fragility play prominent roles in this type of cell death. Hypercontracture can propagate to adjacent cells through gap junctions. More recently, opening of the mitochondrial permeability transition pore has been shown to participate in reperfusion-induced necrosis, although its precise relation with hypercontracture has not been established. Experimental studies have convincingly demonstrated that infarct size can be markedly reduced by therapeutic interventions applied at the time of reperfusion, including contractile blockers, inhibitors of Na(+)/Ca(2+) exchange, gap junction blockers, or particulate guanylyl cyclase agonists. However, in most cases drugs for use in humans have not been developed and tested for these targets, while the effect of existing drugs with potential cardioprotective effect is not well established or understood. Research effort should be addressed to elucidate the unsolved issues of the molecular mechanisms of reperfusion-induced cell death, to identify and validate new targets and to develop appropriate drugs. The potential benefits of limiting infarct size in patients with acute myocardial infarction receiving reperfusion therapy are enormous.
authors.affiliation: Laboratorio de Cardiología Experimental, Servicio de Cardiología, Hospital Universitario Vall d'Hebron, Passeig Vall d'Hebron 119, Barcelona 08035, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Sinovas
authors.forename: Yaser
authors.initials: Y
authors.lastname: Abdallah
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Piper
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
mesh_terms: D000208:Acute Disease; D017209:Apoptosis; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008928:Mitochondria; D009203:Myocardial Infarction / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac; D009336:Necrosis / Q000517:prevention & control*; D012519:Sarcoplasmic Reticulum