Re-expansion pulmonary edema. A potential role for free radicals in its pathogenesis.
Re-expansion pulmonary edema (RPE) has been attributed to decreased lung interstitial pressures from a variety of mechanisms. Because some recent studies have implicated mechanisms that increase microvascular permeability in RPE, we tested whether the edema were due to free radical generation during re-expansion and reoxygenation of the collapsed lung. We used a rabbit model of RPE to test the effects of intracellular (dimethylthiourea) or extracellular (catalase) oxygen metabolite scavengers. Allopurinol was administered separately to determine whether xanthine oxidase was an important source of superoxide in this model. Edema was quantitated both gravimetrically and histologically, and lung xanthine oxidase activity was measured using a sensitive fluorometric assay with pterin as substrate. The results suggest indirectly that OH. or H2O2 (derived from O2-) contribute to the well-documented increase in lung permeability in RPE because dimethylthiourea, dimethylthiourea plus catalase, or catalase alone inhibited the edema to various degrees. Further, we observed histologically that increased numbers of neutrophils were present in re-expanded lungs and that neutrophil infiltration appeared to be diminished by antioxidant administration. Allopurinol did not decrease the edema, because xanthine oxidase activity in rabbit lung tissue is extremely low. We speculate that free radical generation in lung tissue contributes to the pathogenesis of RPE, although reinitiation of lung perfusion and ventilation requires a rapid change in intrathoracic pressure.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D001261:Pulmonary Atelectasis / Q000150:complications / Q000628:therapy; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D002374:Catalase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D013890:Thiourea