Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony.

Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and portions of the pulmonary arteries and veins and right and left ventricles were prepared for scanning and transmission electron microscopy. In ponies that were given only LPS, some areas of pulmonary vascular endothelium appeared normal when compared with untreated controls, but other areas had disoriented endothelial cells or had varying amounts of sloughing, which ranged from focal areas of a few cells to large areas of denuded endothelium. Ponies treated with FM before LPS had less severe and less extensive endothelial cell damage. In both groups, leukocytes were attached to areas of the vessel wall; endothelial cell damage was greater in these regions. Administration of FM before LPS administration attenuated the LPS-induced endothelial cell damage.