Effect of a conjugate of polymyxin B-dextran 70 in horses with experimentally induced endotoxemia.
Abstract: To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses. Methods: 15 horses during study 1 and 6 horses during study 2. Methods: 3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lactate, and prostanoid concentrations. In study 2, horses were given ketoprofen (2.2 mg/kg) or saline solution 15 minutes before infusion of PBD. Fourteen days later, treatments were reversed, using a crossover design. Blood samples were obtained for measurement of thromboxane B2 (TXB2) concentration. Results: For study 1, prior treatment with PBD completely blocked endotoxin-induced changes for heart and respiratory rates, rectal temperature, WBC count, and plasma tumor necrosis factor, interleukin 6, TXB2, and prostaglandin F1 concentrations. There was transient tachypnea, sweating, and increased plasma TXB2 concentration in horses given PBD (with or without LPS). Prior treatment with ketoprofen eliminated all PBD-induced signs and prevented the increase in plasma TXB2 concentration. Conclusions: Signs of endotoxemia were prevented in horses by treatment with PBD, although its use was associated with mild adverse effects. Conclusions: When used in combination with a cyclooxygenase-inhibiting drug, PBD has potential for treatment of horses with endotoxemia.
Publication Date: 1999-01-26 PubMed ID: 9918150
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study explored the effectiveness of a drug called polymyxin B-dextran 70 (PBD) in treating a condition called endotoxemia in horses. The findings reveal that PBD can be an effective treatment for endotoxemia, despite some mild side effects, with these side effects being preventable with concurrent cyclooxygenase-inhibiting drug treatment.
About the Study
- The investigation was carried out in two studies using a total of 21 horses.
- In the first study, 15 horses were divided into three groups. The first and second groups were induced with endotoxemia through the intravenous (IV) administration of lipopolysaccharide (LPS), while the third group received a saline solution.
- PBD was administered to the first and third groups, whereas dextran 70 was given to the second group.
- The efficacy of PBD was assessed by obtained blood samples for hemograms and determining cytokine, lactate, and prostanoid concentrations.
Study 1 Results
- The administration of PBD effectively blocked endotoxemia-induced changes in heart and respiratory rates, rectal temperature, white blood cell count, and certain plasma bio-markers such as tumor necrosis factor, interleukin 6, thromboxane B2, and prostaglandin F1.
- However, some horses given PBD exhibited transient tachypnea (abnormally rapid breathing), sweating, and increased plasma thromboxane B2 concentration- mild adverse side effects of the PBD treatment.
About Study 2
- In the second study, six horses were given PBD along with ketoprofen (an anti-inflammatory medication) or saline solution.
- After a fortnight, the treatments were reversed in a crossover design, and blood samples were obtained to measure thromboxane B2 concentrations.
Study 2 Results
- When used in combination with ketoprofen, all PBD-induced signs and the increase in plasma thromboxane B2 concentration were eliminated.
Conclusions
- The combined use of PBD and a cyclooxygenase-inhibiting drug like ketoprofen has potential as a therapeutic approach for horses suffering from endotoxemia, as PBD effectively prevented signs of endotoxemia while its mild side effects were negated by the concurrent ketoprofen administration.
Cite This Article
APA
MacKay RJ, Clark CK, Logdberg L, Lake P.
(1999).
Effect of a conjugate of polymyxin B-dextran 70 in horses with experimentally induced endotoxemia.
Am J Vet Res, 60(1), 68-75.
Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, University of Florida, Gainesville 32610, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / pharmacology
- Anti-Bacterial Agents / therapeutic use
- Anticoagulants / pharmacology
- Anticoagulants / therapeutic use
- Body Temperature
- Cross-Over Studies
- Cyclooxygenase Inhibitors / pharmacology
- Dextrans / pharmacology
- Dextrans / therapeutic use
- Drug Combinations
- Endotoxemia / drug therapy
- Endotoxemia / veterinary
- Female
- Heart Rate
- Hematocrit / veterinary
- Horse Diseases / drug therapy
- Horses
- Infusions, Intravenous / veterinary
- Interleukin-6 / blood
- Ketoprofen / pharmacology
- Leukocyte Count / veterinary
- Lipid A / metabolism
- Lipopolysaccharides / immunology
- Lipopolysaccharides / pharmacology
- Male
- Polymyxin B / pharmacology
- Polymyxin B / therapeutic use
- Random Allocation
- Thromboxane B2 / blood
- Tumor Necrosis Factor-alpha / analysis
Citations
This article has been cited 4 times.- Mukhopadhyay A, Cook SR, SanMiguel P, Ekenstedt KJ, Taylor SD. TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion. Sci Rep 2023 Jan 27;13(1):1486.
- Hajimohammadi A, Badiei K, Kheibari P, Pourjafar M, Chalmeh A. Effects of Polymyxin B on Clinical Signs, Serum TNF-α, Haptoglobin and Plasma Lactate Concentrations in Experimental Endotoxaemia in Sheep. J Vet Res 2018 Mar;62(1):79-85.
- Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro. Toxins (Basel) 2014 Oct 6;6(10):2962-74.
- Lake P, DeLeo J, Cerasoli F, Logdberg L, Weetall M, Handley D. Pharmacodynamic evaluation of the neutralization of endotoxin by PMX622 in mice. Antimicrob Agents Chemother 2004 Aug;48(8):2987-92.
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