Effect of Indomethacin on Thrombin-Induced Pulmonary Edema in the Rat

Abstract

The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WWDW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, Pa02 decreased progressively and there was a continuous rise in pH and PaC02. An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mgkg body weight, induced a significant further increase in lung weight (p<0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCOz after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Tndomethacin did not prevent the hypoxemia induced by thrombin infusion. In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaC02, it caused lung vascular permeability to protein to increase more than with thrombin alone.