Effect of pentoxifylline, flunixin meglumine, and their combination on a model of endotoxemia in horses.
Abstract: To compare effects of a single dose of pentoxifylline (PTX), flunixin meglumine (FM), and their combination (FM/PTX) in a model of equine endotoxemia. Methods: 24 healthy horses, aged 2 to 15 years. Methods: 4 groups (n = 6/group) received 30 ng of Escherichia coli O55:B5 endotoxin/kg of body weight, i.v., over 30 minutes, and 1 of the following preparations 15 minutes before and 8 hours after endotoxin infusion: FM, 1.1 mg/kg; PTX, 8 mg/kg; FM/PTX, 1.1 mg of FM and 8 mg of PTX/kg; and saline solution bolus (ENDO). Clinical and hematologic variables were measured over 24 hours. Results: Compared with ENDO, FM given before endotoxin significantly reduced TxB2, and 6-keto-PGF1 concentrations, pulse, rectal temperature, and attitude score. Pentoxifylline given before endotoxin resulted in significantly higher 6-keto-PGF1 concentration at 1.5 hours and significantly lower PAI-1 activity at 12 hours. Tumor necrosis factor and IL-6 activities in horses given PTX alone were not significantly different from values in those given the saline bolus. FM/PTX induced effects similar to those of FM alone on endotoxin-induced changes in temperature and TxB2 concentration, and 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group at 1 hour. In horses of the FM group, 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group, from 0.5 hour to 2 hours. Horses of the FM and FM/PTX groups had significantly higher IL-6 activity at 1.5 and 2 hours than did horses of the PTX and ENDO groups; those of the FM and FM/PTX groups had significantly lower WBC count than did those of the PTX and ENDO groups. Conclusions: FM/PTX may help offset deleterious hemodynamic effects of endotoxin more effectively than does either FM or PTX alone.
Publication Date: 1997-11-15 PubMed ID: 9361895
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research studied the effects of pentoxifylline (PTX), flunixin meglumine (FM), and their combination (FM/PTX) in a model of equine endotoxemia, a disease that affects horses. The study concluded that the combined use of FM/PTX in treating equine endotoxemia may offset deleterious hemodynamic effects more effectively than using either FM or PTX alone.
Research Methodology
- A total of 24 healthy horses aged 2 to 15 years participated in the study.
- These horses were divided into four groups, each containing six horses. These groups each received a dose of Escherichia coli O55:B5 endotoxin, and one of FM, PTX, FM/PTX, or a saline solution (ENDO).
- The drugs were administered 15 minutes before and 8 hours after endotoxin infusions.
- Over a 24 hour period, clinical and hematologic variables were measured and observed.
Results of the Research
- Compared to the ENDO group, horses receiving FM prior to endotoxin displayed significantly lowered TxB2, 6-keto-PGF1, pulse and rectal temperature concentrations, and attitude scores.
- Those given PTX showed a significant increase in 6-keto-PGF1 concentration at 1.5 hours and significantly lowered PAI-1 activity at 12 hours. However, the activities of Tumor necrosis factor and IL-6 in horses receiving PTX alone did not differ significantly from those given the saline solution.
- The combination of FM/PTX produced similar effects to FM alone on changes induced by endotoxins in temperature and TxB2 concentration. It yielded a significantly lower 6-keto-PGF1 concentration than horses in the ENDO group after 1 hour.
- Horses in the FM and FM/PTX groups had significantly higher IL-6 activity at 1.5 and 2 hours than those in the PTX and ENDO groups and significantly lower WBC count.
Conclusion of the Study
- The study concluded that using a combination of FM and PTX may help to better offset the adverse hemodynamic effects of endotoxin compared to the use of either FM or PTX alone.
- This finding indicates potential for more effective treatment options for equine endotoxemia, a potentially fatal condition in horses.
Cite This Article
APA
Baskett A, Barton MH, Norton N, Anders B, Moore JN.
(1997).
Effect of pentoxifylline, flunixin meglumine, and their combination on a model of endotoxemia in horses.
Am J Vet Res, 58(11), 1291-1299.
Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / blood
- Analysis of Variance
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
- Body Temperature / drug effects
- Body Temperature / physiology
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Clonixin / therapeutic use
- Disease Models, Animal
- Drug Combinations
- Endotoxemia / drug therapy
- Endotoxemia / physiopathology
- Endotoxemia / veterinary
- Escherichia coli
- Escherichia coli Infections / blood
- Escherichia coli Infections / veterinary
- Hemodynamics / drug effects
- Horse Diseases / blood
- Horse Diseases / drug therapy
- Horse Diseases / physiopathology
- Horses
- Interleukin-6 / blood
- Leukocyte Count / drug effects
- Leukocyte Count / veterinary
- Pentoxifylline / pharmacology
- Pentoxifylline / therapeutic use
- Plasminogen Activator Inhibitor 1 / blood
- Thromboxane B2 / blood
- Time Factors
- Tissue Plasminogen Activator / blood
- Tumor Necrosis Factor-alpha / analysis
- Tumor Necrosis Factor-alpha / metabolism
- Vasodilator Agents / pharmacology
- Vasodilator Agents / therapeutic use
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