Effect of cyclooxygenase inhibition on ethchlorvynol-induced acute lung injury in dogs.
In anesthetized dogs ethchlorvynol (ECV, 9 mg/kg) was selectively administered into the right pulmonary circulation to produce unilateral acute lung injury (ALI) characterized by nonhydrostatic pulmonary edema and systemic hypoxemia. To investigate the hypothesis that products of cyclooxygenase activity are mediators of the arterial hypoxemia, but not the edema formation in this injury, animals were pretreated with one of two chemically dissimilar cyclooxygenase inhibitors, indomethacin (5 mg/kg), or ibuprofen (12.5 mg/kg), or vehicle (0.1 M sodium carbonate) prior to the administration of ECV. Pretreatment with either inhibitor prevented the ECV-induced systemic hypoxemia observed in animals pretreated with vehicle (P less than 0.01). Despite this protection of systemic oxygenation, there was no redistribution of blood flow to the uninjured lung following unilateral ECV administration. Cyclooxygenase inhibition prior to ALI did not attenuate the accumulation of lung water. In the ibuprofen group, left atrial pressure increased significantly following ECV administration. We conclude that a product(s) of cyclooxygenase-mediated arachidonic acid metabolism is responsible for the altered vascular reactivity and consequent systemic hypoxemia in this model, but that the edema formation following ECV is not related to cyclooxygenase activity. In addition, ibuprofen, administered prior to the induction of ALI, exhibits properties not shared by indomethacin but is not different in its capacity to attenuate hypoxemia or in its failure to limit edema formation.
D000818:Animals; D001834:Body Water / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D004285:Dogs; D004984:Ethchlorvynol; D000860:Hypoxia / Q000209:etiology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D055370:Lung Injury; D008297:Male; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000209:etiology
D016861:Cyclooxygenase Inhibitors; D004984:Ethchlorvynol; D010100:Oxygen; D007052:Ibuprofen; D007213:Indomethacin