HISTOLOGIC AND ULTRASTRUCTURAL-CHANGES AFTER LARGE-COLON TORSION, WITH AND WITHOUT USE OF A SPECIFIC PLATELET-ACTIVATING-FACTOR ANTAGONIST (WEB-2086), IN PONIES

The role of platelet-activating factor (PAF) in mediating the colonic damage that develops after large-colon torsion was studied in 14 ponie s. Morphologic changes in areas of the ascending colon and selected ab dominal and thoracic viscera after 1 hour of large-colon torsion and 3 to 5 hours of reperfusion were determined, as well as the protective effects of systemic administration of a specific PAF antagonist (WEB 2 086). Ponies were selected then allocated at random and in equal numbe rs to 2 groups that received 1 of 2 treatments prior to induction of l arge-colon torsion: group 1-control (saline solution), and group 2-WEB 2086 (3 mg/kg of body weight loading dose and 3 mg/kg/h for the remai nder of the study). In each pony, full-thickness tissue specimens from the gastrointestinal tract-cecum, pelvic flexure, left and right vent ral colon, and right dorsal colon-heart, left lung, liver, left adrena l gland, spleen, and right kidney were collected and histologically ev aluated. Edema, mucosal necrosis, and neutrophil infiltration in colon ic sections were graded from 0 (normal) to 3 (most severe changes). Se ctions of liver and lung from 3 ponies in each group, and colon from 1 pony in each group, also were examined by transmission electron micro scopy to determine the presence of ultrastructural alterations. Ischem ia and reperfusion induced marked changes in all sections of colon in all ponies: moderate to severe submucosal edema, moderate necrosis of the superficial epithelium and lamina propria, and necrosis of the muc osal crypt epithelium. Extravascular neutrophil accumulation was evide nt in all sections of colon and cecum, but not in other tissues. Ultra structural lesions were not present in hepatocytes or pneumocytes, or in the endothelial cells of liver, lung, and colon. Bacteria were obse rved by electron microscopy in 5% of hepatic sinusoids. Administration of a specific PAF antagonist, WEB 2086, failed to reduce severity of the observed lesions, indicating that it was not cytoprotective at the dosage used in this model of ischemia-reperfusion injury.