title: Ischemic preconditioning does not protect via blockade of electron transport.
abstract: Ischemic preconditioning (IPC) before sustained ischemia decreases myocardial infarct size mediated in part via protection of cardiac mitochondria. Reversible blockade of electron transport at complex I immediately before sustained ischemia also preserves mitochondrial respiration and decreases infarct size. We proposed that IPC would attenuate electron transport from complex I as a potential effector mechanism of cardioprotection. Isolated, Langendorff-perfused rat hearts underwent IPC (3 cycles of 5-min 37 degrees C global ischemia and 5-min reperfusion) or were perfused for 40 min without ischemia as controls. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated. IPC did not decrease ADP-stimulated respiration measured in intact mitochondria using substrates that donate reducing equivalents to complex I. Maximally expressed complex I activity measured as rotenone-sensitive NADH:ubiquinone oxidoreductase in detergent-solubilized mitochondria was also unaffected by IPC. Thus the protection of IPC does not occur as a consequence of a partial decrease in complex I activity leading to a decrease in integrated respiration through complex I. IPC and blockade of electron transport both converge on mitochondria as effectors of cardioprotection; however, each modulates mitochondrial metabolism during ischemia by different mechanisms to achieve cardioprotection.
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, Case Western Reserve University, OH, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Tanaka-Esposito
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Shadi
authors.initials: S
authors.lastname: Moghaddas
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology; D024101:Mitochondrial Proteins / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D024101:Mitochondrial Proteins; D042967:Electron Transport Complex I