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Veterinary surgery : VS2022; 52(3); 361-369; doi: 10.1111/vsu.13924

Concurrent versus delayed exposure to corticosteroids in equine articular tissues cultured with local anesthetic.

Abstract: To determine the effect of concurrent versus delayed treatment with corticosteroid on equine articular tissues also treated with local anesthetic in vitro in the presence of inflammatory mediators. Methods: Controlled laboratory study. Methods: Five geldings, one mare (aged 3-18 years). Methods: From each horse, 24 synovial and 12 osteochondral explants were cultured in a 12-well plate (2 wells/group, 2 synovial and 1 osteochondral explant/well, total 216 explants in the study). Explants were stimulated in culture medium with 10 μg/ml recombinant equine interleukin-1β and 10 μg/ml tumor necrosis factor-α for 48 hours, then randomly assigned to six treatments: unstimulated control, stimulated control, triamcinolone acetonide (TA, 10  M), mepivacaine hydrochloride (MH, 4.4 mg/ml), MH + TA (concurrent) and MH + TA (delayed). The delayed group was treated with MH and, 6 days later, treated with TA. Every 3 days for 9 days total, medium levels of lactate dehydrogenase (LDH), prostaglandin E (PGE ), matrix metalloproteinase 13 (MMP-13) and glycosaminoglycan (GAG) were quantified via ELISA. Data were analyzed with mixed-effects models with Tukey's multiple comparisons. Results: Stimulation increased medium PGE and MMP-13 and had no effect on LDH or GAG. Treatment with MH increased LDH and decreased PGE and MMP-13. Treatment with TA decreased PGE and MMP-13. Conclusions: There were no differences in cytotoxicity, inflammation or matrix degradation for delayed or concurrent MH and TA treatment groups up to 9 days in culture. Conclusions: The lack of an effect of concurrent versus delayed treatment might indicate that concurrent therapy is acceptable.
© 2022 American College of Veterinary Surgeons.
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Publication Date: 2022-12-26 PubMed ID: 36571324DOI: 10.1111/vsu.13924Google Scholar: Lookup
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  • Randomized Controlled Trial
  • Veterinary
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates whether the timing of corticosteroid treatment has any effect on horse joint tissues that have also been exposed to a local anesthetic, in an inflamed state. The results suggest that there’s no significant difference in tissue damage, inflammation or matrix degradation whether the treatment is simultaneous or delayed.

Study Methodology

The researchers conducted this in a strictly controlled laboratory setting using six horses of varying ages. The horses provided 24 synovial (joint lining tissue) and 12 osteochondral (bone and cartilage) explants (tissue samples cut from the body) each, which were then organized in a precise pattern within a 12-well plate for culture, amounting to a total of 216 explants.

These tissue samples were first treated to generate an inflammatory state through exposure to recombinant equine interleukin-1β and tumor necrosis factor-α. Following this, the samples were randomly assigned to one of six categories for their secondary treatment:

  • An unstimulated control group
  • A stimulated control group
  • Treatment with triamcinolone acetonide (TA), a type of corticosteroid
  • Treatment with mepivacaine hydrochloride (MH), a local anesthetic
  • Concurrent treatment with both MH and TA
  • Delayed treatment, where MH was first applied, followed by TA 6 days later

The researchers kept track of four specific substances in the culture medium covering the tissue samples every three days for nine days: lactate dehydrogenase (LDH), prostaglandin E (PGE ), matrix metalloproteinase 13 (MMP-13) and glycosaminoglycan (GAG). These substances were chosen due to their known roles in cellular health and inflammatory response.

Results and Conclusion

Exposing the tissue samples to inflammation-causing substances increased the medium’s PGE and MMP-13 levels but didn’t affect LDH or GAG levels. The MH treatment resulted in increased LDH (an indicator of cell damage or stress) and reduced levels of PGE and MMP-13 (pro-inflammatory substances).

Treatment with the corticosteroid (TA) led to decreased levels of PGE and MMP-13, signifying its anti-inflammatory effect. The crucial finding was that there was no statistical difference between the groups that received concurrent treatment (MH + TA at the same time) and those that received delayed treatment (MH first, TA after 6 days).

This outcome suggests that whether the corticosteroid is applied concurrently with a local anesthetic or some time afterward, the overall result on the tissue remains the same. Therefore, the use of concurrent treatment could be considered acceptable. The study lays the groundwork for further research into the optimal timing and combination of anti-inflammatory and anesthetic treatments in horses.

Cite This Article

APA
Boorman S, Hanson RR, Velloso Alvarez A, Zhong K, Hofmeister E, Boone LH. (2022). Concurrent versus delayed exposure to corticosteroids in equine articular tissues cultured with local anesthetic. Vet Surg, 52(3), 361-369. https://doi.org/10.1111/vsu.13924

Publication

Veterinary surgery : VS
ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English
Volume: 52
Issue: 3
Pages: 361-369

Researcher Affiliations

Boorman, Sophie
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
Hanson, R Reid
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
Velloso Alvarez, Ana
  • University Cardenal Herrera CEU, Valencia, Spain.
Zhong, Kevin
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
Hofmeister, Erik
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
Boone, Lindsey H
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.

MeSH Terms

  • Horses
  • Animals
  • Male
  • Female
  • Anesthetics, Local / pharmacology
  • Anesthetics, Local / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 13 / pharmacology
  • Cartilage, Articular
  • Adrenal Cortex Hormones / metabolism
  • Adrenal Cortex Hormones / pharmacology
  • Triamcinolone Acetonide / metabolism
  • Triamcinolone Acetonide / pharmacology
  • Glycosaminoglycans / analysis
  • Glycosaminoglycans / metabolism
  • Glycosaminoglycans / pharmacology

References

This article includes 46 references
  1. Clegg P, Booth T. Drugs used to treat osteoarthritis in the horse.. In Pract 2000;22:594-603.
  2. Ireland JL, Wylie CE, Collins SN, Verheyen KLP, Newton JR. Preventive health care and owner-reported disease prevalence of horses and ponies in Great Britain.. Res Vet Sci 2013;95:418-424.
  3. Caron J, Genovese RL. Principals and practices of joint disease treatment.. In: Ross MW, Dyson S, eds. Diagnosis and Management of Lameness in the Horse. 1st ed. Saunders; 2003:746-764.
  4. Moyer W, Schumacher J, Schumacher J. A Guide to Equine Joint Injection and Regional Anesthesia.. 2nd ed. Veterinary Learning Systems; 2007:6-11.
  5. Van Vynckt D, Polis I, Verschooten F, Van Ryssen B. A review of the human and veterinary literature on local anaesthetics and their intra-articular use. Relevant information for lameness diagnosis in the dog.. Vet Comp Orthop Traumatol 2010;23:225-230.
  6. Sherman SL, Khazai RS, James CH, Stoker AM, Flood DL, Cook JL. In vitro toxicity of local anesthetics and corticosteroids on chondrocyte and synoviocyte viability and metabolism.. Cartilage 2015;6:233-240.
  7. Silva GB, De La Côrte FD, Brass KE. Viability of equine chondrocytes after exposure to mepivacaine and ropivacaine in vitro.. J Equine Vet Sci 2019;77:80-85.
  8. Lo IKY, Sciore P, Chung M. Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner.. Art Ther 2009;25:707-715.
  9. Kreuz PC, Steinwachs M, Angele P. Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature.. Knee Surg Sports Traumatol Arthrosc 2018;26:819-830.
  10. Park J, Sutradhar BC, Hong G, Choi SH, Kim G. Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes.. Vet Anaesth Analg 2011;38:127-133.
  11. Zanotto GM, Frisbie DD. Current joint therapy usage in equine practice: changes in the last 10 years.. Equine Vet J 2021;54:750-756.
  12. Caron JP. Intra-articular injections for joint disease in horses.. Vet Clin North Am Equine Pract 2005;21:559-573.
  13. Caron JP, Gandy JC, Schmidt M, Hauptman JG, Sordillo LM. Influence of corticosteroids on interleukin-1beta-stimulated equine chondrocyte gene expression.. Vet Surg 2013;42:231-237.
  14. Barton KI, Chung M, Frank CB, Shrive NG, Hart DA. Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.. Inflamm Res off J Eur Histamine Res Soc 2021;70:99-107.
  15. Trahan RA, Byron CR, Dahlgren LA, Pleasant RS, Werre SR. In vitro effects of three equimolar concentrations of methylprednisolone acetate, triamcinolone acetonide, and isoflupredone acetate on equine articular tissue cocultures in an inflammatory environment.. Am J Vet Res 2018;79:933-940.
  16. Durant TJS, Dwyer CR, McCarthy MBR, Cote MP, Bradley JP, Mazzocca AD. Protective nature of platelet-rich plasma against chondrocyte death when combined with corticosteroids or local anesthetics.. Am J Sports Med 2017;45:218-225.
  17. Frean SP, Cambridge H, Lees P. Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage.. J Vet Pharmacol Ther 2002;25:289-298.
  18. Centeno LM, Moore ME. Preferred intraarticular corticosteroids and associated practice: a survey of members of the American College of Rheumatology.. Arthritis Care Res 1994;7:151-155.
  19. Menon V, Huber C, Portelli A, Baker-Wagner M, Kelley S, Lang K. Patient and physician perspectives guiding intra-articular treatment choice in knee osteoarthritis: stakeholders are aligned on treatment priorities but have different assessments of treatment effect.. J ISAKOS Jt Disord Orthop Sport Med 2021;6:271-276.
  20. Ferris DJ, Frisbie DD, McIlwraith CW, Kawcak CE. Current joint therapy usage in equine practice: a survey of veterinarians 2009.. Equine Vet J 2011;43:530-535.
  21. Bertone AL. Infectious arthritis.. In: Ross MW, Dyson SJ, eds. Diagnosis and Management of Lameness in the Horse. W.B. Saunders; 2003:598-606.
  22. Kay AT, Bolt DM, Ishihara A, Rajala-Schultz PJ, Bertone AL. Anti-inflammatory and analgesic effects of intra-articular injection of triamcinolone acetonide, mepivacaine hydrochloride, or both on lipopolysaccharide-induced lameness in horses.. Am J Vet Res 2008;69:1646-1654.
  23. Blankstein M, Lentine B, Nelms NJ. Common practices in intra-articular corticosteroid injection for the treatment of knee osteoarthritis: a survey of the American Association of hip and Knee Surgeons Membership.. J Arthroplasty 2021;36:845-850.
  24. Seshadri V, Coyle CH, Chu CR. Lidocaine potentiates the chondrotoxicity of methylprednisolone acetate.. Art Ther 2009;25:337-347.
  25. Farkas B, Kvell K, Czömpöly T, Illés T, Bárdos T. Increased chondrocyte death after steroid and local anesthetic combination.. Clin Orthop Relat Res 2010;468:3112-3120.
  26. Kawcak CE. Pathologic manifestations of joint disease.. In: McIlwraith CW, Frisbie DD, Kawcak CE, van Weeren PRBT, eds. Joint Disease in the Horse. 2nd ed. W.B. Saunders; 2016:49-56.
  27. Byron CR, Trahan RA. Comparison of the effects of interleukin-1 on equine articular cartilage explants and cocultures of osteochondral and synovial explants.. Front Vet Sci 2017;4:152.
  28. Haltmayer E, Ribitsch I, Gabner S. Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis.. PLoS One 2019;14:1-19.
  29. Rubio-Martinez LM, Rioja E, Castro Martins M, Wipawee S, Clegg P, Peffers MJ. Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro.. BMC Vet Res 2017;13:318.
  30. Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL. Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source.. Stem Cells Dev 2014;23:1258-1265.
  31. Oke SL, Hurtig MB, Keates RA, Wright JR, Lumsden JH. Assessment of three variations of the 1, 9-dimethylmethylene blue assay for measurement of sulfated glycosaminoglycan concentrations in equine synovial fluid.. Am J Vet Res 2003;64:900-906.
  32. Breu A, Rosenmeier K, Kujat R, Angele P, Zink W. The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage.. Anesth Analg 2013;117:514-522.
  33. Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases.. Clin Immunol 2006;119:229-240.
  34. Mehana E-SE, Khafaga AF, El-Blehi SS. The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review.. Life Sci 2019;234:116786.
  35. Anz A, Smith MJ, Stoker A. The effect of bupivacaine and morphine in a coculture model of diarthrodial joints.. Arthrosc J Arthrosc Relat Surg 2009;25:225-231.
  36. Harkins JD, Carney JM, Tobin T. Clinical use and characteristics of the corticosteroids.. Vet Clin North Am Equine Pract 1993;9:543-562.
  37. Garvican ER, Vaughan-Thomas A, Redmond C, Gabriel N, Clegg PD. MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroids.. J Orthop Res 2010;28:370-378.
  38. Beekhuizen M, Bastiaansen-Jenniskens YM, Koevoet W. Osteoarthritic synovial tissue inhibition of proteoglycan production in human osteoarthritic knee cartilage: establishment and characterization of a long-term cartilage-synovium coculture.. Arthritis Rheum 2011;63:1918-1927.
  39. Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH. Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses.. Equine Vet J 2017;49:107-115.
  40. Kearney CM, Korthagen NM, Plomp SGM. Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation.. Equine Vet J 2020;53:1277-1286.
  41. Frisbie DD, Kawcak CE, Trotter GW, Powers BE, Walton RM, McIlwraith CW. Effects of triamcinolone acetonide on an in vivo equine osteochondral fragment exercise model.. Equine Vet J 1997;29:349-359.
  42. Bolt DM, Ishihara A, Weisbrode SE, Bertone AL. Effects of triamcinolone acetonide, sodium hyaluronate, amikacin sulfate, and mepivacaine hydrochloride, alone and in combination, on morphology and matrix composition of lipopolysaccharide-challenged and unchallenged equine articular cartilage explants.. Am J Vet Res 2008;69:861-867.
  43. D'andrea P, Calabrese A, Grandolfo M. Intercellular calcium signalling between chondrocytes and synovial cells in co-culture.. Biochem J 1998;329(Pt 3):681-687.
  44. Greenberg DD, Stoker A, Kane S, Cockrell M, Cook JL. Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis.. Osteoarthr Cartil 2006;14:814-822.
  45. Velloso Alvarez A, Boone LH, Pondugula SR, Caldwell F, Wooldridge AA. Effects of autologous conditioned serum, autologous protein solution, and triamcinolone on inflammatory and catabolic gene expression in equine cartilage and synovial explants treated with IL-1β in co-culture.. Front Vet Sci 2020;7:323.
  46. Goebel L, Orth P, Müller A. Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4T - comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model.. Osteoarthr Cartil 2012;20:1046-1055.

Citations

This article has been cited 1 times.
  1. Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Front Vet Sci 2023;10:1109473.
    doi: 10.3389/fvets.2023.1109473pubmed: 36876001google scholar: lookup
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