Editorial Type:
Clinical Pathology

Concentrations of thromboxane metabolites in feline urine

Brittany Heggem-Perry Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Stephanie A. Smith Department of Biochemistry, School of Molecular and Cellular Biology, University of Illinois, Urbana, IL 61802.

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Maureen A. McMichael Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Mauria O'Brien Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Anne Saunders Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Jason Tarricone Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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DOI:
https://doi.org/10.2460/ajvr.77.12.1340
Volume/Issue:
Volume 77: Issue 12
Online Publication Date:
01 Dec 2016
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Abstract

OBJECTIVE To determine the predominant thromboxane (TX) metabolite in urine of healthy cats, evaluate whether the method of sample collection would impact concentration of that metabolite, and propose a reference interval for that metabolite in urine of healthy cats.

ANIMALS 17 cats (11 purpose-bred domestic shorthair cats, 5 client-owned domestic shorthair cats, and 1 client-owned Persian cat).

PROCEDURES All cats were deemed healthy on the basis of results for physical examination, a CBC, serum biochemical analysis, urinalysis, and measurement of prothrombin time and activated partial thromboplastin time. Voided and cystocentesis urine samples (or both) were collected. Aliquots of urine were stored at −80°C until analysis. Concentrations of TXB2, 11-dehydroTXB2, and 2,3 dinorTXB2 were measured with commercially available ELISA kits. Urinary creatinine concentration was also measured.

RESULTS 11-dehydroTXB2 was the most abundant compound, representing (mean ± SD) 59 ± 18% of the total amount of TX detected. In all samples, the concentration of 11-dehydroTXB2 was greater than that of 2,3 dinorTXB2 (mean, 4.2 ± 2.7-fold as high). Mean concentration of 11-dehydroTXB2 for the 17 cats was 0.57 ± 0.47 ng/mg of creatinine. A reference interval (based on the 5% to 95% confidence interval) of 0.10 to 2.1 ng of 11-dehydroTXB2/mg of creatinine was proposed for healthy cats.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, 11-dehydroTXB2 was the major TX metabolite in feline urine. Measurement of this metabolite may represent a noninvasive, convenient method for monitoring in vivo platelet activation in cats at risk for thromboembolism.

Abstract

OBJECTIVE To determine the predominant thromboxane (TX) metabolite in urine of healthy cats, evaluate whether the method of sample collection would impact concentration of that metabolite, and propose a reference interval for that metabolite in urine of healthy cats.

ANIMALS 17 cats (11 purpose-bred domestic shorthair cats, 5 client-owned domestic shorthair cats, and 1 client-owned Persian cat).

PROCEDURES All cats were deemed healthy on the basis of results for physical examination, a CBC, serum biochemical analysis, urinalysis, and measurement of prothrombin time and activated partial thromboplastin time. Voided and cystocentesis urine samples (or both) were collected. Aliquots of urine were stored at −80°C until analysis. Concentrations of TXB2, 11-dehydroTXB2, and 2,3 dinorTXB2 were measured with commercially available ELISA kits. Urinary creatinine concentration was also measured.

RESULTS 11-dehydroTXB2 was the most abundant compound, representing (mean ± SD) 59 ± 18% of the total amount of TX detected. In all samples, the concentration of 11-dehydroTXB2 was greater than that of 2,3 dinorTXB2 (mean, 4.2 ± 2.7-fold as high). Mean concentration of 11-dehydroTXB2 for the 17 cats was 0.57 ± 0.47 ng/mg of creatinine. A reference interval (based on the 5% to 95% confidence interval) of 0.10 to 2.1 ng of 11-dehydroTXB2/mg of creatinine was proposed for healthy cats.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, 11-dehydroTXB2 was the major TX metabolite in feline urine. Measurement of this metabolite may represent a noninvasive, convenient method for monitoring in vivo platelet activation in cats at risk for thromboembolism.

Contributor Notes

Address correspondence to Dr. McMichael (mmcm@illinois.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Dec 2016

  • 1. Bills TK, Smith JB, Silver MJ. Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin. J Clin Invest 1977; 60: 1–6.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 2. Marcinkiewicz E, Grodzinska L, Gryglewski RJ. Platelet aggregation and thromboxane A2 formation in cat platelet rich plasma. Pharmacol Res Commun 1978; 10: 1–12.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 3. Ting HJ, Murad JP, Espinosa EV, et al. Thromboxane A2 receptor: biology and function of a peculiar receptor that remains resistant for therapeutic targeting. J Cardiovasc Pharmacol Ther 2012; 17: 248–259.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 4. FitzGerald GA, Pedersen AK, Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 1983; 67: 1174–1177.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 5. Hoh CM, Smith SA, McMichael MA, et al. Evaluation of effects of low-dose aspirin administration on urinary thromboxane metabolites in healthy dogs. Am J Vet Res 2011; 72: 1038–1045.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 6. Roberts LJ II, Sweetman BJ, Oates JA. Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem 1981; 256: 8384–8393.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 7. Catella F, Nowak J, Fitzgerald GA. Measurement of renal and non-renal eicosanoid synthesis. Am J Med 1986; 81: 23–29.

  • 8. Westlund P, Kumlin M, Nordenstrom A, et al. Circulating and urinary thromboxane B2 metabolites in the rabbit: 11-dehydro-thromboxane B2 as parameter of thromboxane production. Prostaglandins 1986; 31: 413–443.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 9. Catella F, Healy D, Lawson JA, et al. 11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation. Proc Natl Acad Sci U S A 1986; 83: 5861–5865.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 10. Kawamura M, Harada Y, Katori M. Evaluation of plasma 11-dehydro-thromboxane B2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals. Thromb Res 1995; 77: 465–474.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 11. Borgeat K, Wright J, Garrod O, et al. Arterial thromboembolism in 250 cats in general practice: 2004–2012. J Vet Intern Med 2014; 28: 102–108.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 12. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med 2003; 17: 73–83.

    • Search Google Scholar
    • Export Citation

  • 13. Butler HC. An investigation into the relationship of an aortic embolus to posterior paralysis in the cat. J Small Anim Pract 1971; 12: 141–158.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 14. Helenski CA, Ross JN Jr. Platelet aggregation in feline cardiomyopathy. J Vet Intern Med 1987; 1: 24–28.

  • 15. Tablin F, Schumacher T, Pombo M, et al. Platelet activation in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2014; 28: 411–418.

  • 16. National Institutes of Health. Guide for the care and use of laboratory animals. 8th ed. Washington, DC: National Academies Press, 2011. Available at: grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf. Accessed January 15, 2014.

    • Search Google Scholar
    • Export Citation

  • 17. Dudley A, Thomason J, Fritz S, et al. Cyclooxygenase expression and platelet function in healthy dogs receiving low-dose aspirin. J Vet Intern Med 2013; 27: 141–149.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 18. Thomason J, Lunsford K, Stokes J, et al. The effects of cyclosporine on platelet function and cyclooxygenase expression in normal dogs. J Vet Intern Med 2012; 26: 1389–1401.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 19. Hall JA, Brockman JA, Jewell DE. Dietary fish oil alters the lysophospholipid metabolomic profile and decreases urinary 11-dehydro thromboxane B(2) concentration in healthy Beagles. Vet Immunol Immunopathol 2011; 144: 355–365.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 20. Maddens BE, Daminet S, Demeyere K, et al. Validation of immunoassays for the candidate renal markers C-reactive protein, immunoglobulin G, thromboxane B2 and retinol binding protein in canine urine. Vet Immunol Immunopathol 2010; 134: 259–264.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 21. Shen L, Matsunami Y, Quan N, et al. In vivo oxidation, platelet activation and simultaneous occurrence of natural immunity in atherosclerosis-prone mice. Isr Med Assoc J 2011; 13: 278–283.

    • Search Google Scholar
    • Export Citation

  • 22. Nakamura A, Nagaya N, Obata H, et al. Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension. Circ J 2013; 77: 2127–2133.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 23. Dharmasaroja PA, Sae-Lim S. Comparison of aspirin response measured by urinary 11-dehydrothromboxane B2 and VerifyNow aspirin assay in patients with ischemic stroke. J Stroke Cerebrovasc Dis 2014; 23: 953–957.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 24. Karon BS, Wockenfus A, Scott R, et al. Aspirin responsiveness in healthy volunteers measured with multiple assay platforms. Clin Chem 2008; 54: 1060–1065.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 25. Baltzer WI, McMichael MA, Ruaux CG, et al. Measurement of urinary 11-dehydro-thromboxane B2 excretion in dogs with gastric dilatation-volvulus. Am J Vet Res 2006; 67: 78–83.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 26. McConnell JP, Cheryk LA, Durocher A, et al. Urinary 11-dehydro-thromboxane B(2) and coagulation activation markers measured within 24 h of human acute ischemic stroke. Neurosci Lett 2001; 313: 88–92.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 27. Norman EJ, Barron RC, Nash AS, et al. Prevalence of low automated platelet counts in cats: comparison with prevalence of thrombocytopenia based on blood smear estimation. Vet Clin Pathol 2001; 30: 137–140.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 28. Davi G, Di Minno G, Coppola A, et al. Oxidative stress and platelet activation in homozygous homocystinuria. Circulation 2001; 104: 1124–1128.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 29. Freese R, Vaarala O, Turpeinen AM, et al. No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects. Eur J Nutr 2004; 43: 175–182.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 30. Cavalca V, Minardi F, Scurati S, et al. Simultaneous quantification of 8-iso-prostaglandin-F(2alpha) and 11-dehydro thromboxane B(2) in human urine by liquid chromatography-tandem mass spectrometry. Anal Biochem 2010; 397: 168–174.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 31. Hishinuma T, Yu GS, Takabatake M, et al. Analysis of the thromboxane/prostacyclin balance in human urine by gas chromatography/selected ion monitoring: abnormalities in diabetics. Prostaglandins Leukot Essent Fatty Acids 1996; 54: 445–449.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 32. Catella F, FitzGerald GA. Paired analysis of urinary thromboxane B2 metabolites in humans. Thromb Res 1987; 47: 647–656.

  • 33. Fitzgerald DJ, Roy L, Catella F, et al. Platelet activation in unstable coronary disease. N Engl J Med 1986; 315: 983–989.

  • 34. Yamanobe S, Nakagawa Y, Hishinuma T, et al. Analysis of urinary 11-dehydrothromboxane B2 in patients with occluded retinal vein using GC/SIM. Prostaglandins Leukot Essent Fatty Acids 1998; 58: 65–68.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 35. Koudstaal PJ, Ciabattoni G, van Gijn J, et al. Increased thromboxane biosynthesis in patients with acute cerebral ischemia. Stroke 1993; 24: 219–223.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 36. Vesterqvist O, Edhag O, Green K, et al. In vivo production of thromboxane in acute human myocardial infarction: a preliminary study. Thromb Res 1985; 37: 459–464.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 37. Brainard BM, Meredith CP, Callan MB, et al. Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs. Am J Vet Res 2007; 68: 251–257.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 38. Cathcart CJ, Brainard BM, Reynolds LR, et al. Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats. J Vet Emerg Crit Care (San Antonio) 2012; 22: 99–106.

    • Search Google Scholar
    • Export Citation

  • 39. Catella F, Lawson JA, Fitzgerald DJ, et al. Analysis of multiple thromboxane metabolites in plasma and urine. Adv Prostaglandin Thromboxane Leukot Res 1987; 17B:611–614.

    • Search Google Scholar
    • Export Citation

  • 40. Westlund P, Granstrom E, Kumlin M, et al. Identification of 11-dehydro-TXB2 as a suitable parameter for monitoring thromboxane production in the human. Prostaglandins 1986; 31: 929–960.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 41. Patrono C, Ciabattoni G, Patrignani P, et al. Evidence for a renal origin of urinary thromboxane B2 in health and disease. Adv Prostaglandin Thromboxane Leukot Res 1983; 11: 493–498.

    • Search Google Scholar
    • Export Citation

  • 42. Welles EG, Boudreaux MK, Crager CS, et al. Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease. Am J Vet Res 1994; 55: 619–627.

    • Search Google Scholar
    • Export Citation

  • 43. Jandrey KE, Norris JW, MacDonald KA, et al. Platelet function in clinically healthy cats and cats with hypertrophic cardiomyopathy: analysis using the Platelet Function Analyzer-100. Vet Clin Pathol 2008; 37: 385–388.

    • Crossref
    • Search Google Scholar
    • Export Citation

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