Biochemical pathways of cell damage during the oxygen paradox of the rat heart.
1. The standard O2-paradox has been studied in the Langendorff-perfused rat heart. 2. Perfusion of glucose-free saline under anoxia did not cause release of creatine kinase (CK) although, it is suggested, there was a progressive rise in [Ca2+]i. 3. Ca(2+)-depletion after anoxia caused CK release. 4. Prolonged anoxic perfusion (55 min) produced a markedly reduced release of CK on Ca(2+)-depletion because, it is suggested, of the reduction in substrates for the release mechanism. 5. No protection against the O2-paradox was found with oxygen radical scavengers and inhibitors. 6. Lowering [Ca2+]o during reoxygenation to 0.1 mM did not reduce CK release. 7. Neither 1 mM amiloride (Na+/H+ antiporter inhibitor) nor 2 x 10(-6) M 1-(5-isoquinolinesulphonyl) piperazine (protein kinase C inhibitor) reduced CK release, unlike their effects in the Ca(2+)-paradox. 8. An hypothesis for events in the O2-paradox in presented: anoxia causes a loss of Ca(2+)-homeostasis and a rise in [Ca2+]i thereby activating a transmembrane NAD(P) oxido-reductase/diaphorase (stage 1); the return of O2 synergistically activates this molecular complex and causes CK release (stage 2).
Daniels
S
S
Department of Environmental and Evolutionary Biology, University of Liverpool, U.K.
Duncan
C J
CJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D015687:Cell Hypoxia; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000209:etiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D007546:Isoquinolines; D010879:Piperazines; D017382:Reactive Oxygen Species; C052422:1-(5-isoquinolinesulfonyl)piperazine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003402:Creatine Kinase