title: Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies.
abstract: Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury. The new concept that mitochondria are not merely stochastic sites of oxidative and calcium-mediated injury but that they activate cellular responses of mitochondrial remodeling and cellular reactions that modulate the balance between cell death and recovery is reviewed, and the therapeutic implications of this concept are discussed.
authors.affiliation: Department of Medicine, Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia 23298; email: edward.lesnefsky@vcuhealth.org , qun.chen@vcuhealth.org.|Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia 23249; email: edward.lesnefsky@va.gov.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
authors.affiliation: Department of Medicine, Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia 23298; email: edward.lesnefsky@vcuhealth.org , qun.chen@vcuhealth.org.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio 44106; email: bernard.tandler@case.edu.
authors.forename: Bernard
authors.initials: B
authors.lastname: Tandler
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106; email: charles.hoppel@case.edu.|Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.|Center for Mitochondrial Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D002317:Cardiovascular Agents
keywords: cardiolipin; electron transport chain; fatty acid oxidation; oxidative phosphorylation; reactive oxygen species; ubiquinol:cytochrome c oxidoreductase