Effects of U-74389G, a novel 21-aminosteroid, on small intestinal ischemia and reperfusion injury in horses.
Abstract: To determine the effects of the 21-aminosteroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (PVO) vascular occlusion during the ischemic period. Methods: TVO: 16 healthy horses were randomly allotted to 3 groups-4 horses received the vehicle alone, 6 horses received a low dosage (3 mg/kg o body weight), and 6 horses a high dosage (10 mg/kg) of U-7438G. PVO: 10 healthy horses were randomly allotted to 2 groups--5 horses received the vehicle alone, and 5 horses received the low dosage (3 mg/kg) of U-74389G. Methods: TVO was induced for 1 hour followed by 2 hours of reperfusion. During PVO, blood flow was reduced to 20% of baseline for 2 hours, followed by 2 hours of reperfusion. For both models, either the vehicle alone or the drug was given 15 minutes prior to reperfusion. Samples were obtained before, during, and after ischemia for determination of myeloperoxidase (MPO) activity, malondealdehyde (MDA) concentration, concentration of conjugated dienes (PVO experiment only), and morphometric analysis. Results: TVO: tissue concentration of MDA and MPO activity were not altered in any group by ischemia or reperfusion. During ischemia, mucosal volume and surface area were reduced. After reperfusion, no further reduction occurred. After initial decrease in submucosal volume during ischemia, there was a significant increase after reperfusion in the vehicle-only group (P < 0.05). PVO: there were no alterations in the concentration of either MDA or conjugated dienes. There was significant increase in the activity of MPO during ischemia and reperfusion (P < 0.05). These effects were similar for the vehicle-only and drug groups. During ischemia, there was a significant decrease in mucosal surface area and volume (P < 0.05), that was continued during reperfusion for the vehicle-only (P < 0.05). Submucosal volume increased during ischemia and reperfusion. Conclusions: Reduced blood flow during ischemia (PVO group) caused continued loss in mucosal volume and surface area during reperfusion. At the dosage given, the 21-aminosteroid, U-74389G, was not effective in preventing continued reduction in mucosal volume and surface area after restoration of blood supply in the horses subjected to reduced blood flow.
Publication Date: 1996-05-01 PubMed ID: 8723896
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- Clinical Trial
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effects of the drug U-74389G on horses’ small intestine after a period of reduced blood flow. The findings indicate that at the administered dosage, U-74389G didn’t prevent further reduction in the volume and surface area of the intestinal lining following restoration of blood flow.
Research Methodology
- The study was conducted on two groups of healthy horses. The first group (TVO) included 16 horses, distributed across three groups: a control group given a vehicle, a group given a low dose of U-74389G, and a group given a high dose of U-74389G. The second group (PVO) included 10 horses divided into a control group and a group receiving a low dose of the drug.
- The TVO (Total Vascular Occlusion) group underwent an induced period of total blood flow stoppage for 1 hour, followed by 2 hours of reperfusion (restoration of blood flow). The PVO (Partial Vascular Occlusion) group had blood flow reduced to 20% for 2 hours, followed again by reperfusion.
- Either the vehicle or U-74389G was administered 15 minutes before reperfusion.
Evaluative Measures
- Samples were taken at different stages of the experiment to measure myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentration, and concentration of conjugated dienes (for the PVO experiment only). These markers indicate oxidative stress and inflammation.
- Structural changes to the intestine, specifically mucosal (interior lining of the intestine) and submucosal (tissue below the intestine lining) volumes and surface areas were also evaluated.
Results
- In the TVO group, neither the MDA concentration nor the MPO activity changed due to ischemia or reperfusion. However, the intestinal mucosal volume and surface area were reduced during ischemia, with no further reduction noted after reperfusion. Interestingly, the submucosal volume significantly increased after reperfusion in the vehicle-only group.
- In the PVO group, no changes were observed in MDA or conjugated diene concentrations. However, MPO activity significantly increased during ischemia and reperfusion, indicating inflammation. Moreover, reductions in mucosal surface area and volume were sustained during reperfusion in the vehicle-only group, and submucosal volume increased during both processes.
Conclusion
- The study concluded that reduced blood flow during ischemia caused a continuous loss of mucosal volume and surface area during reperfusion. However, the drug U-74389G, at the tested dosage, was not effective in preventing this reduction after the restoration of blood flow.
Cite This Article
APA
Vatistas NJ, Snyder JR, Hildebrand SV, Harmon FA, Woliner MJ, Barry SJ, Nieto J, Henry P, Enos LR, Magliano D, Brown SA, Drake C.
(1996).
Effects of U-74389G, a novel 21-aminosteroid, on small intestinal ischemia and reperfusion injury in horses.
Am J Vet Res, 57(5), 762-770.
Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, University of California, Davis 95616, USA.
MeSH Terms
- Animals
- Antioxidants / administration & dosage
- Antioxidants / therapeutic use
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Horse Diseases / drug therapy
- Horse Diseases / pathology
- Horse Diseases / physiopathology
- Horses
- Infusions, Intravenous / veterinary
- Intestinal Mucosa / blood supply
- Intestinal Mucosa / chemistry
- Intestinal Mucosa / physiology
- Jejunum / blood supply
- Jejunum / chemistry
- Jejunum / physiology
- Male
- Malondialdehyde / analysis
- Mesenteric Vascular Occlusion / drug therapy
- Mesenteric Vascular Occlusion / physiopathology
- Mesenteric Vascular Occlusion / veterinary
- Peroxidase / analysis
- Pregnatrienes / administration & dosage
- Pregnatrienes / therapeutic use
- Reperfusion Injury / drug therapy
- Reperfusion Injury / physiopathology
- Reperfusion Injury / veterinary
- Time Factors
Citations
This article has been cited 4 times.- Grages AM, Verhaar N, Pfarrer C, Breves G, Burmester M, Neudeck S, Kästner S. Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine.. Animals (Basel) 2022 Aug 22;12(16).
- Verhaar N, de Buhr N, von Köckritz-Blickwede M, Hewicker-Trautwein M, Pfarrer C, Mazzuoli-Weber G, Schulte H, Kästner S. Ischaemic postconditioning reduces apoptosis in experimental jejunal ischaemia in horses.. BMC Vet Res 2021 Apr 26;17(1):175.
- Faleiros RR, Macoris DG, Alves GE, Souza DG, Teixeira MM, Moore RM. Local and remote lesions in horses subjected to small colon distension and decompression.. Can J Vet Res 2008 Jan;72(1):68-76.
- Sharifi K, Mostaghni K, Maleki M, Badiei K. Ischaemia/reperfusion injury in experimentally induced abomasal volvulus in sheep.. Vet Res Commun 2007 Jul;31(5):575-90.
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