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

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.

Controlled laboratory study.

Five geldings, one mare (aged 3-18 years).

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^-6  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 E₂ (PGE₂ ), matrix metalloproteinase 13 (MMP-13) and glycosaminoglycan (GAG) were quantified via ELISA. Data were analyzed with mixed-effects models with Tukey's multiple comparisons.

Stimulation increased medium PGE₂ and MMP-13 and had no effect on LDH or GAG. Treatment with MH increased LDH and decreased PGE₂ and MMP-13. Treatment with TA decreased PGE₂ and MMP-13.

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.

The lack of an effect of concurrent versus delayed treatment might indicate that concurrent therapy is acceptable.