Effects of the 21-aminosteroid U-74389G on ischemia and reperfusion injury of the ascending colon in horses

Nicholas J. Vatistas From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Jack R. Snyder From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Susan V. Hildebrand From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Faye A. Harmon From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Michael J. Woliner From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Pegeen Henry From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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L. Reed Enos From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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David Magliano From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Scott Anthony Brown From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Christiana Drake From the Veterinary Medical Teaching Hospital (Vatistas, Henry, Enos), and Departments of Surgery (Snyder, Hildebrand, Harmon, Woliner), Veterinary Anatomy (Magliano) and Department of Statistics (Drake), School of Veterinary Medicine, University of California, Davis, CA 95616, and The Upjohn Co (Brown), Kalamazoo, MI 49001.

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Summary

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 ischemia, full-thickness colonic tissue biopsy specimens were obtained for measurement of malondealdehyde (mda) concentration and myeloperoxidase activity and for morphologic evaluation.

Although increases were not significant, mda concentration and myeloperoxidase activity increased during 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 myeloperoxidase activity at 30 and 60 minutes of reperfusion.

In horses of the vehicle-only group, ischemia induced a decrease in mucosal surface area that was continued into the reperfusion period (P ≤ 0.05). Administration of U-74389G at both dosages (3 and 10 mg/kg) prevented 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 all groups, mucosal volume increased for the initial 60 minutes of reperfusion.

Our results indicate that lipid peroxidation may be partially involved in continued cellular death after ischemia of the ascending colon of horses. The 21-aminosteroid, U-74389G, prevented further loss of mucosa and partially attenuated the induced increase in myeloperoxidase activity during reperfusion of the ascending colon.

Summary

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 ischemia, full-thickness colonic tissue biopsy specimens were obtained for measurement of malondealdehyde (mda) concentration and myeloperoxidase activity and for morphologic evaluation.

Although increases were not significant, mda concentration and myeloperoxidase activity increased during 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 myeloperoxidase activity at 30 and 60 minutes of reperfusion.

In horses of the vehicle-only group, ischemia induced a decrease in mucosal surface area that was continued into the reperfusion period (P ≤ 0.05). Administration of U-74389G at both dosages (3 and 10 mg/kg) prevented 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 all groups, mucosal volume increased for the initial 60 minutes of reperfusion.

Our results indicate that lipid peroxidation may be partially involved in continued cellular death after ischemia of the ascending colon of horses. The 21-aminosteroid, U-74389G, prevented further loss of mucosa and partially attenuated the induced increase in myeloperoxidase activity during reperfusion of the ascending colon.

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