Pulmonary oxygen toxicity in the guinea pig. Effect of indomethacin

Deleterious pulmonary effects of hyperoxia are thought, in part, to be mediated by high-energy radicals and inflammatory reactions. It has been suggested that arachidonate metabolites, such as leukotrienes, may be responsible for the latter mechanism. We sought to demonstrate that concurrent exposure to hyperoxia and indomethacin, a potent inhibitor of cyclooxygenase, would increase pulmonary inflammation. A total of 50 female guinea pigs were treated as pairs with 95.6% oxygen or air and separately with 0.3 mg/kg of indomethacin or normal saline every 12 h for 3 days. A significant increase in leukocytes in bronchopulmonary lavage subsequent to combined oxygen and indomethacin treatment was observed when compared with either oxygen, indomethacin, or air treatments alone (p less than 0.05). Although oxygen treatment did alter pulmonary volume-pressure relations (p less than 0.05), hyperoxia alone or with concurrent indomethacin treatment did not alter elastance or histologic structures. These findings suggest that pulmonary inflammation in response to hyperoxia may be augmented by indomethacin. We speculate that increased lipoxygenase products of arachidonate metabolism may be partially responsible for these changes.