EFFECT OF IBUPROFEN ON THROMBIN-INDUCED PULMONARY-EDEMA IN THE RAT

The effect of ibuprofen on thrombin-induced pulmonary edema was studie d in rats. Thrombin infusion produced a significant increase in lung w eight, wet weight/dry weight ratio tend relative lung water content, a rise in mean pulmonary arterial pressure and a fall in mean systemic arterial pressure. It also caused a progressive decrease in PaO2 and a continuous increase in pH and PaCO2. Administration of either the S-i somer or R-isomer of ibuprofen at doses of 5 mg/kg body weight prior t o thrombin infusion resulted in significant reduction in lung weight, wet weight/dry weight ratio and water content. The wet weight/dry weig ht ratio and the water content were somewhat lower after infusion of t he S-isomer than of the R-isomer. Ibuprofen diminished the thrombin-in duced increase in mean pulmonary arterial pressure and attenuated the early and late decrease in mean systemic arterial pressure caused by t hrombin. Ibuprofen also stabilized thrombin-indnced impairments in PaO 2, PaCO2 and pH. The results thus indicate that ibuprofen effectively counteracts hemodynamic changes, stabilizes impairments in arterial bl ood gas variables and attenuates the increase in lung vascular permeab ility to protein with pulmonary edema caused by thrombin, The results also indicate a substantial R to S chiral inversion of ibuprofen in vi vo in the rat.