title: Cyclooxygenase expression and platelet function in healthy dogs receiving low-dose aspirin.
abstract: BACKGROUND
  Low-dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are nonresponsive to the antiplatelet effects of aspirin ("aspirin resistance").
  
  
  OBJECTIVE
  That low-dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression.
  
  
  METHODS
  Twenty-four healthy dogs.
  
  
  METHODS
  A repeated measures study. Platelet function (PFA-100 closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) were evaluated before and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, nonresponders, and inconsistent responders.
  
  
  RESULTS
  Low-dose aspirin increased closure times significantly (62% by Day 10, P < .001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, -29.7-136.1%) (P = .047) and 72% on Day 10 (range, -0.37-210%) (P < .001). Platelet COX-2 MFI increased significantly by 34% (range, -29.2-270%) on Day 3 (P = .003) and 74% (range, -19.7-226%) on Day 10 (P < .001). Urinary 11-dTXB(2) concentrations significantly (P = .005, P < .001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production.
  
  
  CONCLUSIONS
  Low-dose aspirin consistently inhibits platelet function in approximately one-third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. COX isoform expression before treatment did not predict aspirin resistance.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dudley
authors.forename: J
authors.initials: J
authors.lastname: Thomason
authors.forename: S
authors.initials: S
authors.lastname: Fritz
authors.forename: J
authors.initials: J
authors.lastname: Grady
authors.forename: J
authors.initials: J
authors.lastname: Stokes
authors.forename: R
authors.initials: R
authors.lastname: Wills
authors.forename: L
authors.initials: L
authors.lastname: Pinchuk
authors.forename: A
authors.initials: A
authors.lastname: Mackin
authors.forename: K
authors.initials: K
authors.lastname: Lunsford
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D001241:Aspirin