Blockade of electron transport during ischemia protects cardiac mitochondria.
Subsarcolemmal mitochondria sustain progressive damage during myocardial ischemia. Ischemia decreases the content of the mitochondrial phospholipid cardiolipin accompanied by a decrease in cytochrome c content and a diminished rate of oxidation through cytochrome oxidase. We propose that during ischemia mitochondria produce reactive oxygen species at sites in the electron transport chain proximal to cytochrome oxidase that contribute to the ischemic damage. Isolated, perfused rabbit hearts were treated with rotenone, an irreversible inhibitor of complex I in the proximal electron transport chain, immediately before ischemia. Rotenone pretreatment preserved the contents of cardiolipin and cytochrome c measured after 45 min of ischemia. The rate of oxidation through cytochrome oxidase also was improved in rotenone-treated hearts. Inhibition of the electron transport chain during ischemia lessens damage to mitochondria. Rotenone treatment of isolated subsarcolemmal mitochondria decreased the production of reactive oxygen species during the oxidation of complex I substrates. Thus, the limitation of electron flow during ischemia preserves cardiolipin content, cytochrome c content, and the rate of oxidation through cytochrome oxidase. The mitochondrial electron transport chain contributes to ischemic mitochondrial damage that in turn augments myocyte injury during subsequent reperfusion.
Lesnefsky
Edward J
EJ
Department of Medicine, Division of Cardiology, School of Dentistry, Case Western Reserve University, Cleveland, Ohio 44106, USA. EXL9@po.cwru.edu
Chen
Qun
Q
Moghaddas
Shadi
S
Hassan
Medhat O
MO
Tandler
Bernard
B
Hoppel
Charles L
CL
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016877:Oxidants / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012402:Rotenone / Q000378:metabolism; D014475:Uncoupling Agents / Q000378:metabolism
D002308:Cardiolipins; D016877:Oxidants; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I