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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.
Publication Date: 2022-12-26 PubMed ID: 36571324DOI: 10.1111/vsu.13924Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Randomized Controlled Trial
- Veterinary
- Journal Article
Summary
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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
Researcher Affiliations
- Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
- Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
- University Cardenal Herrera CEU, Valencia, Spain.
- Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
- Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
- 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
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Citations
This article has been cited 1 times.- 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.
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