title: The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion.
abstract: Our understanding of the end-effectors involved in preconditioning protection is still very limited. This is partially due to an incomplete knowledge of the mechanisms responsible for acute sarcolemmal rupture and cell death during the first minutes of reperfusion, including the relative roles of hypercontracture-mediated sarcolemmal rupture and mitochondrial permeability transition pore (MPTP) opening-mediated cell death. In the present article, the role of proposed end-effectors of preconditioning protection, defined as molecules directly involved in cell death that are modified by ischemic preconditioning (IP), is examined. IP attenuates hypercontracture-mediated cell death, probably through several mechanisms, including attenuated calpain activation during reperfusion leading to preserved cytoskeletal integrity and accelerated recovery of Na+/K+-ATPase function, but probably also protein kinase G (PKG)-mediated improved calcium handling. The potential role of gap junctions in preconditioning protection is controversial, but the recently discovered mitochondrial localisation of connexin43 seems to play an important role in protection that has not yet been completely defined. Several recent studies suggest that IP can reduce MPTP opening during reperfusion and limit infarct size through this mechanism, although the contribution of this widely accepted mechanism to the infarct size reduction induced by IP in the intact heart needs to be established.
authors.affiliation: Servicio de Cardiologia, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain. dgdorado@vhebron.net
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodriguez-Sinovas
authors.forename: Marisol
authors.initials: M
authors.lastname: Ruiz-Meana
authors.forename: Javier
authors.initials: J
authors.lastname: Inserte
authors.forename: Luis
authors.initials: L
authors.lastname: Agulló
authors.forename: Alberto
authors.initials: A
authors.lastname: Cabestrero
mesh_terms: D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D006801:Humans; D015640:Ion Channel Gating; D019157:Ischemic Preconditioning, Myocardial; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002118:Calcium