Role of reactive oxygen species in reperfusion injury of the rabbit lung.
We have developed a model of reperfusion injury in Krebs buffer-perfused rabbit lungs, characterized by pulmonary vasoconstriction, microvascular injury, and marked lung edema formation. During reperfusion there was a threefold increase in lung superoxide anion (O2-) production, as measured by in vivo reduction of nitroblue tetrazolium, and a twofold increase in the release of O2- into lung perfusate, as measured by reduction of succinylated ferricytochrome c. Injury could be prevented by the xanthine oxidase inhibitor allopurinol, the O2- scavenger SOD, the hydrogen peroxide scavenger catalase, the iron chelator deferoxamine, or the thiols dimethylthiourea or N-acetylcysteine. The protective effect of SOD could be abolished by the anion channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid, indicating that SOD consumes O2- in the extracellular medium, thereby creating a concentration gradient favorable for rapid diffusion of O2- out of cells. Our results extend information about the mechanisms of reperfusion lung injury that have been assembled by studies in other organs, and offer potential strategies for improved organ preservation, for treatment of reperfusion injury after pulmonary thromboembolectomy, and for explanation and therapy of many complications of pulmonary embolism.
Kennedy
T P
TP
Department of Medicine, University of Tennessee Center for Health Sciences, Memphis 38163.
Rao
N V
NV
Hopkins
C
C
Pennington
L
L
Tolley
E
E
Hoidal
J R
JR
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004195:Disease Models, Animal; D005609:Free Radicals; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000502:physiology*; D013481:Superoxides / Q000502:physiology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D003574:Cytochrome c Group; D005609:Free Radicals; D007473:Ion Channels; D013481:Superoxides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D009580:Nitroblue Tetrazolium; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid