Xanthine oxidase-derived oxygen radicals induce pulmonary edema via direct endothelial cell injury.
Pulmonary hypoperfusion/ischemia-reperfusion (I/R) may initiate ARDS (nonhydrostatic pulmonary edema). Endothelial damage via xanthine oxidase (XO)-derived oxygen radicals (O2*) may mediate I/R injury. We previously documented Factor VIII antigen (F8) as a marker for endothelial injury. The purpose of this study was to (1) document I/R-induced nonhydrostatic pulmonary edema, (2) identify whether XO or O2* mediates nonhydrostatic edema, and (3) identify the site of injury (? endothelium). Rat lungs were isolated, ventilated, and perfused (100 min, control, or 40 min at 37 degrees C, I (static vent.), + 60 min, R). Effluent was analyzed for F8 release (ELISA: data relative to control). Tungsten-fed rats had negligible lung XO vs rats fed standard diet (3.6 vs 34.5 mU/g, (P less than 0.05). Catalase (CAT) 50 micrograms/ml) was added to perfusate prior to R. Sectioned lungs were fluorescein anti-F8 photographed (IF) and qualitatively assessed. (Table: see text). We conclude that (1) pulmonary hypoperfusion (I/R) leads to nonhydrostatic pulmonary edema, and (2) the edema results in part from XO-generated O2* directed at the capillary endothelium.
Grosso
M A
MA
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Brown
J M
JM
Viders
D E
DE
Mulvin
D W
DW
Banerjee
A
A
Velasco
S E
SE
Repine
J E
JE
Harken
A H
AH
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002199:Capillary Permeability; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D005169:Factor VIII / Q000276:immunology / Q000378:metabolism; D005609:Free Radicals; D008168:Lung / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism*; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism*; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014841:von Willebrand Factor
D000941:Antigens; D005609:Free Radicals; D014841:von Willebrand Factor; D005169:Factor VIII; D002374:Catalase; D014969:Xanthine Oxidase; D010100:Oxygen; D014414:Tungsten