The role of
cyclooxygenase products in
acute lung injury was determined by pretreatment of dogs with
ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only,
lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with
ibuprofen. The comparison of gravimetric and
indicator-dilution measurements of
edema fluid indicates that
edema fluid could not be reliably detected
after treatment with
ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the
ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of
edema, venous admixture was significantly less in the group treated with
ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that
ibuprofen inhibited
cyclooxygenase activity without affecting
lipoxygenase activity. These results suggest that in intact dogs
ibuprofen has a protective effect on both pulmonary gas transfer and
pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.