title: Effects of clopidogrel on horses with experimentally induced endotoxemia.
abstract: OBJECTIVE
  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.
authors: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850.
authors: Ashlee E
authors: AE
authors: Watts
authors: Sally L
authors: SL
authors: Ness
authors: Thomas J
authors: TJ
authors: Divers
authors: Susan L
authors: SL
authors: Fubini
authors: Amelia H
authors: AH
authors: Frye
authors: Tracy
authors: T
authors: Stokol
authors: Kevin J
authors: KJ
authors: Cummings
authors: Marjory B
authors: MB
authors: Brooks
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature; D000077144:Clopidogrel; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry / Q000662:veterinary; D006339:Heart Rate / Q000187:drug effects; D006734:Horse Diseases / Q000097:blood* / Q000503:physiopathology*; D006736:Horses; D008070:Lipopolysaccharides / Q000008:administration & dosage; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D056152:Respiratory Rate / Q000187:drug effects; D013916:Thrombelastography / Q000662:veterinary; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine