Effects of clopidogrel on horses with experimentally induced endotoxemia.
Abstract: To evaluate the effects of clopidogrel on clinical and clinicopathologic variables in healthy horses with experimentally induced endotoxemia. Methods: 12 adult mares. Procedures-Horses were assigned with a randomization procedure to receive clopidogrel (4 mg/kg, once, then 2 mg/kg, q 24 h; n = 6) or a placebo (6) through a nasogastric tube. After 72 hours of treatment, horses received lipopolysaccharide (LPS; 30 ng/kg, IV). Heart rate, respiratory rate, rectal temperature, CBC variables, plasma fibrinogen concentration, serum tumor necrosis factor-α concentration, plasma von Willebrand factor concentration, and measures of platelet activation (including ADP- and collagen-induced platelet aggregation and closure times, thrombelastography variables, and results of flow cytometric detection of platelet membrane P-selectin, phosphatidylserine, and microparticles) were determined at various times before and after LPS administration by investigators unaware of the treatment groups. Statistical analyses were performed with repeated-measures ANOVA. Results: 4 of 6 clopidogrel-treated horses had significant decreases in ADP-induced platelet aggregation before and after LPS administration. Heart rate increased significantly after LPS administration only for the placebo group. No significant differences were detected between groups for CBC variables, closure time, and plasma concentration of fibrinogen or serum concentration of tumor necrosis factor-α, and no clinically relevant differences were detected for other hemostatic variables. Conclusions: In this study, administration of LPS did not induce platelet hyperreactivity in horses on the basis of measures of platelet adhesion, aggregation, degranulation, and procoagulant activity. Administration of clopidogrel was associated with variable platelet antiaggregatory activity and attenuated some clinical signs of endotoxemia.
Publication Date: 2014-07-26 PubMed ID: 25061708DOI: 10.2460/ajvr.75.8.760Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research tested the effects of the drug clopidogrel on horses with experimentally induced endotoxemia, a condition characterized by the presence of endotoxins in the blood. It found that clopidogrel reduced platelet activity and some clinical symptoms of endotoxemia.
Methodology
- The experiment involved 12 adult mares randomly assigned to receive either clopidogrel or a placebo through a nasogastric tube.
- The dose given was 4 mg/kg initially, then 2 mg/kg every 24 hours for a total of 72 hours.
- Following this, all horses were exposed to lipopolysaccharide (LPS), a bacterial endotoxin, to induce endotoxemia.
- A range of variables were then measured at different times before and after the administration of LPS. These included heart and respiratory rates, rectal temperature, complete blood count (CBC) variables, plasma fibrinogen concentration, serum tumor necrosis factor-α concentration, and a range of measures of platelet activation. Investigators were not aware of which horses were in which treatment group.
Results
- The study found that the horses treated with clopidogrel showed significant decreases in ADP-induced platelet aggregation both before and after exposure to LPS.
- After the administration of LPS, heart rate only increased significantly for the placebo group, suggesting an effect of clopidogrel in controlling heart rate under endotoxemic conditions.
- No significant differences were observed between the treatment and placebo groups in terms of CBC variables, closure time, and the plasma concentration of fibrinogen or the serum concentration of tumor necrosis factor-α.
- For other haemostatic variables, the differences between groups were also not clinically relevant.
Conclusions
- The research concluded that in this sample, lipopolysaccharide (LPS) administration did not induce platelet hyperreactivity in horses, based on the measures of platelet adhesion, aggregation, degranulation, and procoagulant activity used.
- However, treatment with clopidogrel was associated with variable antiplatelet activity and did appear to reduce some clinical signs of endotoxemia.
Cite This Article
APA
Watts AE, Ness SL, Divers TJ, Fubini SL, Frye AH, Stokol T, Cummings KJ, Brooks MB.
(2014).
Effects of clopidogrel on horses with experimentally induced endotoxemia.
Am J Vet Res, 75(8), 760-769.
https://doi.org/10.2460/ajvr.75.8.760 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850.
MeSH Terms
- Analysis of Variance
- Animals
- Body Temperature
- Clopidogrel
- Endotoxemia / blood
- Endotoxemia / drug therapy
- Endotoxemia / veterinary
- Female
- Fibrinogen / metabolism
- Flow Cytometry / veterinary
- Heart Rate / drug effects
- Horse Diseases / blood
- Horse Diseases / physiopathology
- Horses
- Lipopolysaccharides / administration & dosage
- P-Selectin / metabolism
- Platelet Activation / drug effects
- Platelet Aggregation Inhibitors / administration & dosage
- Respiratory Rate / drug effects
- Thrombelastography / veterinary
- Ticlopidine / administration & dosage
- Ticlopidine / analogs & derivatives
- Tumor Necrosis Factor-alpha / blood
- von Willebrand Factor / metabolism
Citations
This article has been cited 1 times.- Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA. Activated platelets and platelet-leukocyte aggregates in the equine systemic inflammatory response syndrome. J Vet Diagn Invest 2022 May;34(3):448-457.
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