Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia.
Abstract: Platelet-activating factor (PAF) is an important mediator of endotoxaemia and various PAF receptor antagonists prevent many of the adverse effects of experimental endotoxaemia in laboratory animals. In this study a specific PAF receptor antagonist was used to investigate the role of PAF in equine endotoxaemia. At an interval of not greater than 10 days, 6 horses were each challenged with endotoxin and endotoxin with concurrent administration of SRI 63-441, a PAF receptor antagonist. The order of the treatments was randomised. Clinical signs, serum biochemical and coagulation profiles, and platelet aggregation in vitro were monitored in all horses for 24 h after treatment. Challenge with endotoxin increased maximal platelet aggregation induced by PAF. This response was blocked by administration of SRI 63-441 concurrently with endotoxin. No changes in percentage maximal platelet aggregation to ADP or collagen were noted after administration of endotoxin. The PAF receptor antagonist delayed the onset of fever, tachycardia, leucopenia and lactic acidaemia. Lack of more profound beneficial alterations of the horses' responses to endotoxin may have been due to the low dose of endotoxin administered in this model or to only partial effectiveness of SRI 63-441 in blocking the effects of endotoxin-induced PAF.
Publication Date: 1993-03-01 PubMed ID: 8385601DOI: 10.1111/j.2042-3306.1993.tb02927.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research studies the effect of a platelet-activating factor (PAF) receptor antagonist on horses suffering from endotoxaemia. The study concludes that the administration of the PAF antagonist results in a delay in the onset of several symptoms such as fever, tachycardia, leucopenia, and lactic acidaemia, suggesting a beneficial effect.
Study Overview and Methodology
- The research investigated the importance of platelet-activating factor (PAF) in equine endotoxaemia. Endotoxaemia is a condition involving the presence of endotoxins, toxic substances released when bacteria die and disintegrate, in the blood.
- The experiment involved six horses that were exposed to endotoxin, along with simultaneous administration of a specific PAF receptor antagonist known as SRI 63-441, within a period of no more than 10 days.
- The study was conducted in a randomized order and monitored for 24 hours after the treatment for changes in clinical signs, serum biochemical and coagulation profiles, and platelet aggregation in vitro.
Key Findings and Interpretations
- The administration of the PAF receptor antagonist significantly impacted the role of PAF in equine endotoxaemia. A notable effect was seen on platelet aggregation, which is the clustering of platelets in the blood. After endotoxin challenge, it was observed that PAF-induced maximum platelet aggregation increased. However, it was blocked when the antagonist, SRI 63-441, was administered with the endotoxin.
- There were no significant alterations in the percentage maximum platelet aggregation to adenosine diphosphate (ADP) or collagen after the administration of the endotoxin.
- The antagonist played a role in delaying the onset of several significant symptoms of endotoxaemia such as fever, tachycardia (a heart rate that exceeds the normal resting rate), leucopenia (a decrease in the number of white blood cells), and lactic acidaemia (excessive acid in the body due to the production of lactic acid).
Caveats and Considerations
- The researchers proposed that the limited effectiveness in altering the response of horses to endotoxin could be due to the low dose of endotoxin administered in this study or due to the partial effectiveness of the PAF receptor antagonist SRI 63-441 in blocking the effects of endotoxin-induced PAF.
Cite This Article
APA
Carrick JB, Morris DD, Moore JN.
(1993).
Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia.
Equine Vet J, 25(2), 152-157.
https://doi.org/10.1111/j.2042-3306.1993.tb02927.x Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
MeSH Terms
- Animals
- Antithrombin III / analysis
- Blood Pressure / drug effects
- Body Temperature / drug effects
- Endotoxins / blood
- Heart Rate / drug effects
- Hematocrit / veterinary
- Horse Diseases / chemically induced
- Horse Diseases / drug therapy
- Horses
- Leukocyte Count / drug effects
- Leukocyte Count / veterinary
- Platelet Activating Factor / antagonists & inhibitors
- Platelet Aggregation / drug effects
- Platelet Membrane Glycoproteins
- Quinolinium Compounds / pharmacology
- Quinolinium Compounds / therapeutic use
- Receptors, Cell Surface / antagonists & inhibitors
- Receptors, G-Protein-Coupled
- Thromboxane B2 / blood
- Tumor Necrosis Factor-alpha / analysis
Citations
This article has been cited 1 times.- Steiner AA, Romanovsky AA. Platelet-activating factor is a potent pyrogen and cryogen, but it does not mediate lipopolysaccharide fever or hypothermia. Temperature (Austin) 2015 Oct-Dec;2(4):535-42.
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