title: Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control. Role of oxygen-free radicals and cardiolipin.
abstract: Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocites. Mitochondrial respiration is an important source of ROS generation and hence a potential contributor to cardiac reperfusion injury. Appropriate treatment strategy could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. In the present study, we examined the effect of lowering the oxygen tension, at the onset of the reperfusion, on various parameters of mitochondrial bioenergetics in rat heart tissue. After isolation of mitochondria from control, ischemic, normoxic and hypoxic reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production and in addition, the degree of lipid peroxidation, cardiolipin content and cardiolipin oxidation. We found that normoxic reperfusion significantly altered all these mitochondrial parameters, while hypoxic reperfusion had a protective effect attenuating these alterations. This effect appears to be due, at least in part, to a reduction of mitochondrial ROS generation with subsequent preservation of cardiolipin integrity, protection of mitochondrial function and improvement of post-ischemic hemodynamic function of the heart.
authors.affiliation: Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics, via E. Orabona, 4, 70126 Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Petrosillo
authors.forename: N
authors.initials: N
authors.lastname: Di Venosa
authors.forename: F M
authors.initials: FM
authors.lastname: Ruggiero
authors.forename: M
authors.initials: M
authors.lastname: Pistolese
authors.forename: D
authors.initials: D
authors.lastname: D'Agostino
authors.forename: E
authors.initials: E
authors.lastname: Tiravanti
authors.forename: T
authors.initials: T
authors.lastname: Fiore
authors.forename: G
authors.initials: G
authors.lastname: Paradies
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism* / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide; D015227:Lipid Peroxidation; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D005609:Free Radicals; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D010100:Oxygen