EFFECTS OF THE 21-AMINOSTEROID U-74389G ON ISCHEMIA AND REPERFUSION INJURY OF THE ASCENDING COLON IN HORSES

Sixteen horses were allotted at random to 3 groups: vehicle only; low dosage (vehicle and 3 mg of U-74389G/kg of body weight); high dosage ( vehicle and 10 mg of U-74389G/kg). These solutions were given prior to reperfusion. The ascending colon was subjected to 2 hours of ischemia followed by 2 hours of reperfusion. Before, during, and after ischemi a, full-thickness colonic tissue biopsy specimens were obtained for me asurement of malondealdehyde (MDA) concentration and myeloperoxidase a ctivity and for morphologic evaluation. Although increases were not si gnificant, MDA concentration and myeloperoxidase activity increased du ring ischemia and reperfusion. Administration of U-74389G did not have significant effects on MDA concentration and myeloperoxidase activity . However, the lower dosage tended (P = 0.08) to reduce myeloperoxidas e activity at 30 and 60 minutes of reperfusion. In horses of the vehic le-only group, ischemia induced a decrease in mucosal surface area tha t was continued into the reperfusion period (P less than or equal to 0 .05). Administration of U-74389G at both dosages (3 and 10 mg/kg) prev ented the reperfusion-induced reduction in mucosal surface area, which was significant at 60 minutes (high dosage; P = 0.05) and 90 minutes (low and high dosages; P = 0.02). After initial reduction in horses of ah groups, mucosal volume increased for the initial 60 minutes of rep erfusion. Our results indicate that lipid peroxidation may be partiall y involved in continued cellular death after ischemia of the ascending colon of horses. The 21-aminosteroid, U-74389G, prevented further los s of mucosa and partially attenuated the induced increase in myelopero xidase activity during reperfusion of the ascending colon.