Effects of dimethyl sulfoxide, allopurinol, 21-aminosteroid U-74389G, and manganese chloride on low-flow ischemia and reperfusion of the large colon in horses.
Abstract: Thirty horses were randomly assigned to 1 of 5 groups. All horses were anesthetized and subjected to ventral midline celiotomy, then the large colon was exteriorized and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and was maintained for 3 hours. Colonic blood flow was then restored, and the colon was reperfused for an additional 3 hours. One of 5 drug solutions was administered via the jugular vein 30 minutes prior to colonic reperfusion: group 1, 0.9% NaCl; group 2, dimethyl sulfoxide: 1 g/kg of body weight; group 3, allopurinol: 25 mg/kg; group 4, 21-aminosteroid U-74389G: 10 mg/kg; and group 5, manganese chloride (MnCl2): 10 mg/kg. Hemodynamic variables were monitored and recorded at 30-minutes intervals. Systemic arterial, systemic venous (SV), and colonic venous (CV) blood samples were collected for measurement of blood gas tensions, oximetry, lactate concentration, PCV, and plasma total protein concentration. The eicosanoids, 6-keto prostaglandin F1 alpha, prostaglandin E2, and thromboxane B2, were measured in CV blood, and endotoxin was measured in CV and SV blood. Full-thickness biopsy specimens were harvested from the left ventral colon for histologic evaluation and determination of wet weight-to-dry weight ratios (WW:DW). Data were analyzed, using two-way ANOVA for repeated measures, and statistical significance was set at P < 0.05. Heart rate, mean arterial pressure, and cardiac output increased with MnCl2 infusion; heart rate and cardiac output remained increased throughout the study, but mean arterial pressure returned to BL values within 30 minutes after completion of MnCl2 infusion. Other drug-induced changes were not significant. There were significant increases in mean pulmonary artery and mean right atrial pressures at 2 and 2.5 hours in horses of all groups, but other changes across time or differences among groups were not observed. Mean pulmonary artery pressure remained increased through 6 hours in all groups, but mean right atrial pressure had returned to BL values at 3 hours. Mean colonic arterial pressure was significantly decreased at 30 minutes of ischemia and remained decreased through 6 hours; however, by 3.25 hours it was significantly higher than the value at 3 hours of ischemia. Colonic arterial resistance decreased during ischemia and remained decreased throughout reperfusion in all groups; there were no differences among groups for colonic arterial resistance.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Date: 1995-05-01 PubMed ID: 7661465
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- Clinical Trial
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research involves studying the effects of four different substances on blood flow in the large colon of horses during a situation of low-flow ischemia and subsequent reperfusion. By varying the drug administered and comparing results, the study aims to gain a clearer understanding of the effects of each in such a circumstance.
Methodology
- The researchers worked with a sample of 30 horses, which were randomly divided into 5 groups. Every horse was anesthetized and underwent ventral midline celiotomy (surgical incision along the midline of the abdomen), and their large colon was exteriorized (pulled out) and installed with instruments.
- Colonic arterial blood flow in the horses was reduced to 20% of the baseline value, and this low-flow condition was maintained for 3 hours. After this period of controlled ischemia (restricted blood flow), reperfusion or restoration of blood flow to the colon was also controlled for an additional 3 hours.
- Half an hour before the start of the reperfusion phase, one of 5 drug solutions was administered through the jugular vein of the horses in the different groups. The solutions were 0.9% NaCl (control group), dimethyl sulfoxide, allopurinol, 21-aminosteroid U-74389G, and manganese chloride.
Data Collection and Analysis
- Several physiological variables like heart rate, blood pressure and cardiac output were monitored in the horses, and data recorded at half-hour intervals.
- Blood samples from various circulatory systems – systemic arterial, systemic venous (SV) and colonic venous (CV) – were collected to measure parameters like gas tension, lactate concentration, packed cell volume (PCV), plasma total protein concentration and three types of eicosanoids.
- The presence of endotoxin was measured in CV and SV blood samples.
- Biopsy specimens were harvested from the left ventral colon for histological examination and calculation of wet weight-to-dry weight ratios.
- The data obtained was statistically analyzed using two-way ANOVA, with P < 0.05 set as the statistical significance threshold.
Findings
- Upon infusion with manganese chloride, there was an increase in heart rate, arterial pressure, and cardiac output. While the increased heart rate and cardiac output remained consistent throughout the study, arterial pressure returned to baseline values within 30 minutes post-infusion.
- Other changes induced by the other drugs were considered non-significant.
- Significant increases in mean pulmonary artery pressure and mean right atrial pressures were observed at 2 and 2.5 hours in horses from all groups, but no other time-based changes or group-based differences were seen.
- In all groups, the colonic arterial pressure significantly decreased at 30 minutes of ischemia and remained low even 6 hours later. However, it was found to be significantly higher than the value at 3 hours of ischemia by the 3.25 hours mark.
- Colonic arterial resistance was reduced during ischemia and remained reduced throughout reperfusion in all groups, with no group-wise differences.
Cite This Article
APA
Moore RM, Muir WW, Bertone AL, Beard WL, Stromberg PC.
(1995).
Effects of dimethyl sulfoxide, allopurinol, 21-aminosteroid U-74389G, and manganese chloride on low-flow ischemia and reperfusion of the large colon in horses.
Am J Vet Res, 56(5), 671-687.
Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Ohio State University, Columbus 43210-1089, USA.
MeSH Terms
- Allopurinol / pharmacology
- Analysis of Variance
- Animals
- Antioxidants / pharmacology
- Chlorides / pharmacology
- Colon / blood supply
- Colon / drug effects
- Dimethyl Sulfoxide / pharmacology
- Endotoxins / analysis
- Hemodynamics / physiology
- Horses
- Manganese Compounds / pharmacology
- Peroxidase / metabolism
- Pregnatrienes / pharmacology
- Reperfusion Injury / prevention & control
- Reperfusion Injury / veterinary
Grant Funding
- R01-DK43780 / NIDDK NIH HHS
Citations
This article has been cited 2 times.- Chen L, Cai P, Cheng Z, Zhang Z, Fang J. Pharmacological postconditioning with atorvastatin calcium attenuates myocardial ischemia/reperfusion injury in diabetic rats by phosphorylating GSK3β. Exp Ther Med 2017 Jul;14(1):25-34.
- 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.
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