Indomethacin and dexamethasone decrease oleic acid-induced pulmonary protein leak in rabbits

Similarities between oleic acid (OA)-induced pulmonary injury and clinical adult respiratory distress syndrome (ARDS) have resulted in extensive use of this model. Using technetium 99m (Tc-99m)-labeled human serum albumin (Tc-HSA) we examined the effect of indomethacin (a prostaglandin synthetase inhibitor) and dexamethasone (a corticosteroid) alone and in combination on OA-induced pulmonary protein leak. Computer-acquired dynamic gamma camera imaging before (15 min), during, and after (60 min) OA infusion were used to generate time-activity curves for lung and heart regions. A lung:heart activity ratio curve with a positive slope indicates pulmonary capillary protein leak of the labeled substance. Tc-99m labeling of red blood cells followed by OA injury showed no significant change in slope, indicating that lung hemorrhage was not being measured; however, Tc-HSA showed significant protein leakage following OA injury. Pretreatment with indomethacin or dexamethasone did not significantly alter either the preinsult or the postinsult slope. Combined pretreatment with indomethacin and dexamethasone significantly decreased, but did not eliminate, the pulmonary protein leak produced by OA injury. Our results indicate that multiple factors are involved in the production of the pulmonary capillary leak in OA-induced lung injury. In addition to the possible therapeutic efficacy of combined corticosteroids and nonsteroidal antiinflammatory drugs, our results demonstrate that these substances may be useful in defining the pathophysiology involved in permeability pulmonary edema.