Effects of the 21-aminosteroid U-74389G on ischemia and reperfusion injury of the ascending colon in horses.
Abstract: 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 < or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1993-12-01 PubMed ID: 8116953
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- Clinical Trial
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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This research paper investigates the effect of the drug U-74389G on injuries caused by lack of blood supply and subsequent restoration of blood supply (ischemia and reperfusion) in the ascending colon of horses. It found that U-74389G had no significant effect on inflammation markers, but it did help preserve the surface area of the colon’s mucosal layer during the reperfusion period.
Study Design and Methodology
- Sixteen horses were randomly divided into three groups for the experiment, subjected to different dosages of solutions containing the drug U-74389G: one group received only vehicle (control), a second group received a low dosage of the drug (3mg/kg) and the last group received a high dosage (10mg/kg).
- The solutions were administered prior to the reperfusion stage, after the ascending colon of each horse had undergone 2 hours of ischemia.
- Throughout this process, biopsies of full-thickness colonic tissue were taken at various intervals for further analysis.
Measurements and Findings
- The tissue samples were analyzed for concentration of malondealdehyde (MDA) and myeloperoxidase activity, both used as indicators of inflammation and resultant tissue damage related to ischemia and reperfusion.
- MDA concentration and myeloperoxidase activity were found to be increased during the ischemia and reperfusion stages, but not by a statistically significant amount. Administration of U-74389G did not significantly affect these indicators.
- However, the lower dosage of the drug was observed to have a tendency to reduce myeloperoxidase activity during the initial stages of reperfusion.
- In the vehicle-only group, reduced mucosal surface area of the colon was observed due to ischemia and continued into the reperfusion period.
- Administration of both low and high dosages of U-74389G prevented this reduction in mucosal surface area during reperfusion, which was statistically significant at certain intervals.
- For all groups, an initial reduction in mucosal volume was observed, which then increased in the first 60 minutes of reperfusion.
Conclusions
- While the 21-aminosteroid U-74389G did not have a significant effect on the MDA concentration and myeloperoxidase activity (key markers of inflammation), its administration did seem to have a protective effect on the mucosal surface area during the reperfusion stage, suggesting that it may offer some protection against ischemia-reperfusion injury in the colon.
Cite This Article
APA
Vatistas NJ, Snyder JR, Hildebrand SV, Harmon FA, Woliner MJ, Henry P, Enos LR, Magliano D, Brown SA, Drake C.
(1993).
Effects of the 21-aminosteroid U-74389G on ischemia and reperfusion injury of the ascending colon in horses.
Am J Vet Res, 54(12), 2155-2160.
Publication
Researcher Affiliations
- Veterinary Medical Teaching Hospital, Davis, CA.
MeSH Terms
- Analysis of Variance
- Animals
- Antioxidants / therapeutic use
- Biopsy
- Colon / blood supply
- Colon / pathology
- Female
- Horse Diseases
- Horses
- Ischemia / drug therapy
- Ischemia / metabolism
- Ischemia / veterinary
- Male
- Malondialdehyde / analysis
- Peroxidase / metabolism
- Pregnatrienes / therapeutic use
- Reperfusion Injury / drug therapy
- Reperfusion Injury / metabolism
- Reperfusion Injury / veterinary
- Time Factors
Citations
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