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Platelet-activating factor and not thromboxane A2 is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro.

Abstract: Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The effects of quinacrine on platelet aggregation in citrated platelet-rich plasma induced by ADP and platelet-activating factor were also investigated. CV-3988 and WEB2086 caused a concentration-dependent inhibition of endotoxin-induced aggregation. The non-steroidal anti-inflammatories were without effect except flunixin meglumine which produced a small inhibition of endotoxin-induced aggregation. Quinacrine had a similar effect to the platelet-activating factor antagonists, but also non-competitively inhibited platelet aggregation in citrated platelet-rich plasma. It is concluded that platelet-activating factor is a critical mediator of endotoxin-induced platelet aggregation in the horse, but that products of cyclo-oxygenase metabolism are not of importance.
Publication Date: 1996-03-01 PubMed ID: 8735817DOI: 10.1097/00001721-199603000-00021Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article explores the role of platelet-activating factor in endotoxin-induced platelet aggregation in horse blood, concluding that it is of critical importance, while cyclo-oxygenase metabolism products are not.

Objective of the Study

  • This study was performed to analyze the roles of platelet-activating factor and the by-products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) in mediating the effect of endotoxin on platelet aggregation in equine heparinised whole blood.

Method Used

  • The researchers investigated the effects of various drugs on endotoxin-induced aggregation. These drugs include aspirin, flunixin meglumine, and carprofen (all of which are non-steroidal anti-inflammatory drugs), CV-3988 and WEB2086 (both are platelet-activating factor receptor antagonists), and quinacrine (a phospholipase A2 inhibitor).
  • The team also examined the effects of quinacrine on platelet aggregation in citrated platelet-rich plasma caused by ADP and platelet-activating factor.

Key Findings

  • The study identified that CV-3988 and WEB2086 caused a concentration-dependent inhibition of endotoxin-induced aggregation.
  • The non-steroidal anti-inflammatory drugs did not have any significant effect on endotoxin-induced aggregation, except for flunixin meglumine, which showed slight inhibition.
  • Quinacrine not only demonstrated similar effects to the platelet-activating factor antagonists, but also inhibited platelet aggregation in citrated platelet-rich plasma non-competitively.

Conclusion

  • The study concluded that the platelet-activating factor plays a vital role in endotoxin-induced platelet aggregation in horse blood.
  • However, the role of the by-products of cyclo-oxygenase metabolism in the same process was deemed not significant.

Cite This Article

APA
Jarvis GE, Evans RJ. (1996). Platelet-activating factor and not thromboxane A2 is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro. Blood Coagul Fibrinolysis, 7(2), 194-198. https://doi.org/10.1097/00001721-199603000-00021

Publication

ISSN: 0957-5235
NlmUniqueID: 9102551
Country: England
Language: English
Volume: 7
Issue: 2
Pages: 194-198

Researcher Affiliations

Jarvis, G E
  • Department of Clinical Veterinary Medicine, University of Cambridge, UK.
Evans, R J

    MeSH Terms

    • Animals
    • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
    • Aspirin / pharmacology
    • Azepines / pharmacology
    • Carbazoles / pharmacology
    • Clonixin / analogs & derivatives
    • Clonixin / pharmacology
    • Endotoxins / pharmacology
    • Heparin
    • Horses
    • In Vitro Techniques
    • Phospholipases A / antagonists & inhibitors
    • Phospholipases A2
    • Phospholipid Ethers / pharmacology
    • Platelet Activating Factor / metabolism
    • Platelet Aggregation / drug effects
    • Platelet Aggregation Inhibitors / pharmacology
    • Quinacrine / pharmacology
    • Thromboxane A2 / metabolism
    • Triazoles / pharmacology

    Citations

    This article has been cited 1 times.
    1. Goulding DR, Myers PH, Goulding EH, Blankenship TL, Grant MF, Forsythe DB. The effects of perioperative analgesia on litter size in Crl:CD1(ICR) mice undergoing embryo transfer. J Am Assoc Lab Anim Sci 2010 Jul;49(4):423-6.
      pubmed: 20819387