Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipin.
Ischemia and reperfusion result in mitochondrial dysfunction, with decreases in oxidative capacity, loss of cytochrome c, and generation of reactive oxygen species. During ischemia of the isolated perfused rabbit heart, subsarcolemmal mitochondria, located beneath the plasma membrane, sustain a loss of the phospholipid cardiolipin, with decreases in oxidative metabolism through cytochrome oxidase and the loss of cytochrome c. We asked whether additional injury to the distal electron chain involving cardiolipin with loss of cytochrome c and cytochrome oxidase occurs during reperfusion. Reperfusion did not lead to additional damage in the distal electron transport chain. Oxidation through cytochrome oxidase and the content of cytochrome c did not further decrease during reperfusion. Thus injury to cardiolipin, cytochrome c, and cytochrome oxidase occurs during ischemia rather than during reperfusion. The ischemic injury leads to persistent defects in oxidative function during the early reperfusion period. The decrease in cardiolipin content accompanied by persistent decrements in the content of cytochrome c and oxidation through cytochrome oxidase is a potential mechanism of additional myocyte injury during reperfusion.
Division of Cardiology, Department of Medicine, School of Dental Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. EXL9@cwru.edu
Edward J
EJ
Lesnefsky
Qun
Q
Chen
Thomas J
TJ
Slabe
Maria S K
MS
Stoll
Paul E
PE
Minkler
Medhat O
MO
Hassan
Bernard
B
Tandler
Charles L
CL
Hoppel
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000378:metabolism / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits; D012119:Respiration; D012508:Sarcolemma / Q000378:metabolism
D002308:Cardiolipins; D010743:Phospholipids; D045304:Cytochromes c; D003576:Electron Transport Complex IV