Veterinary Research Communications

, Volume 18, Issue 3, pp 217–224 | Cite as

Preliminary observations on the effects of Meloxicam in a new model for acute intra-articular inflammation in dogs

  • H. van Bree
  • C. Justus
  • J. F. Quirke
Pharmacology

Abstract

The effects of intra-articular injection, on two occasions, 3 weeks apart, of the contrast agent Urografin on the cytological and biochemical characteristics of synovial fluid (SF) were examined in two studies in dogs. The first study provided baseline data in two non-medicated dogs. The second study used a cross-over design whereby 4 dogs received a 7-day oral treatment with either a placebo or meloxicam (0.2 mg/kg body weight daily) with a washout period of 3 weeks, in order to determine the effect of this new non-steroidal anti-inflammatory drug (NSAID) on the response to Urografin injection. SF samples were collected under general anaesthesia prior to and at 24 and 72 h after each Urografin injection. The volume, relative viscosity, white blood cell count and concentrations of protein, lactate dehydrogenase (LDH) and hyaluronic acid of these samples were determined.

The results from both studies indicate that intra-articular injection of Urografin provoked a mild local transient inflammatory response, the most dramatic evidence of which was an increase in the white blood cell count in the SF after 24 h. In the second study, comparison of the synovial fluid measurements of the placebo-treated dogs at 24 h after Urografin injection with those prior to injection revealed significant increases in SF volume, white blood cell count, protein concentration and LDH activity and a significant reduction in relative viscosity. At 72 h after injection, only the white blood cell count and relative viscosity were significantly different from the pre-injection values. All of these measurements were, however, associated with high coefficients of variation, which must be taken into account in assessing the usefulness of the model for drug-testing purposes. Nevertheless, the administration of meloxicam significantly reduced the SF volume and white blood cell count at 24 h relative to the effects of concurrent placebo treatment. The general health status of the animals was not disturbed at any time as assessed by clinical and haematological observations. No adverse reactions were observed.

Keywords

arthritis contrast medium dog inflammation meloxicam model NSAID synovial fluid 

Abbreviations

LDH

lactate dehydrogenase

NSAID

non-steroidal anti-inflammatory drug

SF

synovial fluid

WBC

white blood cell count

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bettmann, M.A., 1989. Adverse events and contrast media: scope of the problem. In: I. Enge and J. Edgren (eds),Patient Safety and Adverse Events in Contrast Medium Examinations, (Elsevier Science Publishers BV, Amsterdam) 1–8Google Scholar
  2. Bruner, L.H., 1992. Alternatives to the use of animals in household products and cosmetic testing.Journal of the American Veterinary Medical Association,200, 669–673Google Scholar
  3. Busch, B., 1975.Veterinary Laboratory Manual, 1 (Heinemann Medical Books, London), 113–167Google Scholar
  4. Chang, Y.H., 1972. Studies on phagocytosis. II. The effect of nonsteroidal anti-inflammatory use on phagocytosis and on urate crystal-induced canine joint inflammation.Journal of Pharmacology and Experimental Therapeutics,183, 235–244Google Scholar
  5. Corbetti, F., Malatesta, V., Camposampiero, A., Mazzi, A., Punzi, L., Angelini, F., Vigo, M. and Todesco, S., 1986. Effects of various contrast media and epinephrine on synovial fluid.Radiology,161, 195–198Google Scholar
  6. Covino, B.G., Dubner, R., Gybels, J., Kosterlitz, H.W., Liebeskind, J.C., Sternbach, R.A., Vyklickzy, L., Yamamura, H. and Zimmermann, M., 1980. Ethical standards for the investigations of experimental pain in animals.Pain,9, 141–143Google Scholar
  7. Dresser, R., 1992. Standards for animal research: Justification and assessment of alternatives.Journal of the American Veterinary Medical Association,200, 667–669Google Scholar
  8. Firth, E.C., Wensing, T. and Seuren, F., 1987. An induced synovitis disease model in ponies.Cornell Veterinarian,77, 107–118Google Scholar
  9. Grant, G.H. and Kachmar, J.F., 1982. The proteins of body fluids. In: N.W. Tietz (ed.),Fundamentals of Clinical Chemistry, 2nd edn, (WB Saunders, Philadelphia), 363–364Google Scholar
  10. Hadler, N.M., Spitznagel, J.K. and Quintet, R.J., 1979. Lysosomal enzymes in inflammatory synovial effusions.Journal of Immunology,123, 572–577Google Scholar
  11. Hall, F.M., Goldberg, R.P., Wyshak, G. and Kilcoyne, R.F., 1985. Shoulder arthrography: comparison of morbidity after use of various contrast media.Radiology,154, 339–341Google Scholar
  12. Higgs, G.A., Harvey, E.A., Ferreira, S.H. and Vane, J.R., 1976. The effects of antiinflammatory drugs on the production of prostaglandinsin vivo. In: B. Samuelsson and R. Paoletti (eds.),Advances in Prostaglandin and Thromboxane Research, vol. 1, (Raven Press, New York), 105Google Scholar
  13. Higgins, A.J., Lees, P. and Sedgwick, A.D., 1987. Development of equine models of inflammation.The Veterinary Record,120, 517–522Google Scholar
  14. Johansen, J.G. and Berner, A., 1976. Arthrography with Amipaque (metrizamide) and other contrast media: a roentgenographic and histologic evaluation in rabbits.Investigative Radiology,11, 534–537Google Scholar
  15. Lipowitz, A.J., 1985. Synovial fluid. In: C.D. Newton and D.M. Nunamaker (eds.),Textbook of Small Animal Orthopedics, (J.B. Lippincott, Philadelphia), 1015–1028Google Scholar
  16. May, S.A., Lees, P., Higgins, A.J. and Sedgwick, A.D., 1987. Inflammation: A clinical perspective.The Veterinary Record,120, 514–517Google Scholar
  17. Moncada, S., Ferreira, S.H. and Vane, J.R., 1975. Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint.European Journal of Pharmacology,31, 250–260Google Scholar
  18. Naib, Z.M., 1973. Cytology of synovial fluids.Acta Cytologica,17, 299–309Google Scholar
  19. Niemegeers, C.J.E. and Janssen, P.A.J., 1975. Suprofen, a potent antagonist of sodium urate crystal-induced arthritis in dogs.Arzneimittel Forschung,25, 1512–1515Google Scholar
  20. Pastershank, S.P., Resnick, D., Niwayama, G., Danzig, L. and Haghighi, P., 1982. The effect of water-soluble contrast media on the synovial membrane.Radiology,143, 331–334Google Scholar
  21. Pruzansky, W., Russell, M.L., Gordon, D.A. and Ogryzlo, M.A., 1973. Serum and synovial fluid proteins in rheumatoid arthritis and degenerative joint diseases.American Journal of Medical Science,265, 483–490Google Scholar
  22. Ropes, M.W. and Bauer, W., 1953.Synovial Fluid Changes in Joint Disease, (Harvard University Press, Cambridge, MA)Google Scholar
  23. SAS, SAS/STAT User's Guide, Release 6.03 Edition, (SAS Institute Inc., Cary, NC)Google Scholar
  24. SCE, 1974. The committee on enzymes of the Scandinavian society for clinical chemistry and clinical physiology (SCE).Scandinavian Journal of Clinical Laboratory Investigation,33, 291–306Google Scholar
  25. Smith, R.L., Gilkerson, E., Kohatsu, N., Merchant, T. and Schurman, D.J., 1980. Quantitative microanalysis of synovial fluid and articular cartilage glycosaminoglycans.Analytical Biochemistry,103, 191–200Google Scholar
  26. Torbeck, R.L. and Prieur, D.J., 1979. Plasma and synovial fluid lysozyme activity in horses with experimental cartilage defects.American Journal of Veterinary Research,40, 1531–1536Google Scholar
  27. van Bree, H., 1989. Epinephrine enhanced positive contrast shoulder arthrography in the dog.Journal of Veterinary Medicine,36, 687–691Google Scholar
  28. van Bree, H., Verhaeghe, B. and Maenhout, D., 1989. Positive contrast arthrography of the dog's shoulder with meglumine-sodium diatrizoate.Journal of Veterinary Medicine,36, 421–430Google Scholar
  29. van Bree, H., van Ryssen, B., Tshamala, M. and Maenhout, T., 1992. Comparison of the nonionic contrast agents lopromide and lotrolan for positive contrast arthrography of the scapulohumeral joint in dogs.American Journal of Veterinary Research,53, 1622–1626Google Scholar
  30. Vyklicky, L., 1979. Techniques for the study of pain in animals. In: J.J. Bonica (ed.),Advances in Pain Research and Therapy, vol. 3, (Raven Press, New York), 727–745Google Scholar
  31. Winter, C.A., Risley, E.A. and Nuss, G.W., 1962. Carrageenin-induced edema in hind paw of rat as an assay for anti-inflammatory drugs.Proceedings of the Society for Experimental Biology and Medicine,11, 544Google Scholar

Copyright information

© Kluwer Academic Publishers bv 1994

Authors and Affiliations

  • H. van Bree
    • 1
  • C. Justus
    • 2
  • J. F. Quirke
    • 2
  1. 1.The Clinic for Small AnimalsUniversity of GentGentBelgium
  2. 2.Boehringer Ingelheim Vetmedica GmbH Int.Ingelheim am RheinGermany

Personalised recommendations