Effects of hylan on amphotericin-induced carpal lameness in equids

J. G. Peloso From the Department of Large Animal Clinical Sciences (Peloso JG, Stick, Caron), and the Department of Biomechanics (Soutas-Little), Michigan State University, East Lansing, MI 48824-1314, (517) 353-9710 and the Rheumatology Division of the Wellesley Hospital, (Peloso PM) Toronto, Ontario.

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J. A Stick From the Department of Large Animal Clinical Sciences (Peloso JG, Stick, Caron), and the Department of Biomechanics (Soutas-Little), Michigan State University, East Lansing, MI 48824-1314, (517) 353-9710 and the Rheumatology Division of the Wellesley Hospital, (Peloso PM) Toronto, Ontario.

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J. P. Caron From the Department of Large Animal Clinical Sciences (Peloso JG, Stick, Caron), and the Department of Biomechanics (Soutas-Little), Michigan State University, East Lansing, MI 48824-1314, (517) 353-9710 and the Rheumatology Division of the Wellesley Hospital, (Peloso PM) Toronto, Ontario.

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P. M. Peloso From the Department of Large Animal Clinical Sciences (Peloso JG, Stick, Caron), and the Department of Biomechanics (Soutas-Little), Michigan State University, East Lansing, MI 48824-1314, (517) 353-9710 and the Rheumatology Division of the Wellesley Hospital, (Peloso PM) Toronto, Ontario.

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R. WC Soutas-Little From the Department of Large Animal Clinical Sciences (Peloso JG, Stick, Caron), and the Department of Biomechanics (Soutas-Little), Michigan State University, East Lansing, MI 48824-1314, (517) 353-9710 and the Rheumatology Division of the Wellesley Hospital, (Peloso PM) Toronto, Ontario.

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Summary

In this double-blind study, the effectiveness of and dose response to intra-articular administration of modified hyaluronan (hylan) was determined in an equine carpal lameness model over a 23-day period, using a computerized three-dimensional motion analysis system, synovial fluid variables, and synovial histologic examination.

In 24 clinically sound horses, baseline motion data was acquired from horses trotting at 4 m/s on a high-speed treadmill. Then, to induce lameness, 25 mg of amphotericin B in 5 ml of sterile water was injected into the left middle carpal joint of each horse every other day for 3 treatments. Phenybutazone (2.2 mg/kg of body weight, PO, once) and butorphanol tartrate (0.1 mg/kg, IM, q 6 h, for 36 hours) were used to control signs of discomfort. Horses were assigned at random to 4 equal groups and received intracarpal administration of either 1, 2, 4 ml of hylan (8 mg/ml), or 2 ml of balanced electrolyte solution (control).

Intracarpal administration of amphotericin B caused significant (P ≤ 0.01) increase in subjective lameness grades over the 2-week evaluation period, and hylan administration did not significantly (P ≤ 0.01) change the subjective lameness grade. Lameness induction caused significant (P ≤ 0.01) decrease in head and withers excursions during the lame forelimb support phase and significant (P ≤ 0.05) increase in head and withers excursions during the sound forelimb support phase. Synovitis induction was further characterized by significant (P ≤ 0.05) increases in total wbc, polymorphonuclear, and large and small mononuclear cell numbers, and synovial fluid total protein concentrations. Also, subjective scores for synovial sections were significantly (P ≤ 0.05) different from baseline values, but hylan treatment at the 1-, 2-, or 4-ml dose did not significantly (P ≤ 0.05) alter these variables, compared with baseline values or values in control horses. Hyaluronan concentrations were not altered by induction of synovitis or hylan treatment.

Although clinical use of hyaluronan for treatment of traumatic joint disease in horses is well accepted, the beneficial effect of hylan was not detectable in this study. Further studies are required to more fully characterize the possible beneficial effects of hyaluronan-based products for treatment of joint disease in equids.

Summary

In this double-blind study, the effectiveness of and dose response to intra-articular administration of modified hyaluronan (hylan) was determined in an equine carpal lameness model over a 23-day period, using a computerized three-dimensional motion analysis system, synovial fluid variables, and synovial histologic examination.

In 24 clinically sound horses, baseline motion data was acquired from horses trotting at 4 m/s on a high-speed treadmill. Then, to induce lameness, 25 mg of amphotericin B in 5 ml of sterile water was injected into the left middle carpal joint of each horse every other day for 3 treatments. Phenybutazone (2.2 mg/kg of body weight, PO, once) and butorphanol tartrate (0.1 mg/kg, IM, q 6 h, for 36 hours) were used to control signs of discomfort. Horses were assigned at random to 4 equal groups and received intracarpal administration of either 1, 2, 4 ml of hylan (8 mg/ml), or 2 ml of balanced electrolyte solution (control).

Intracarpal administration of amphotericin B caused significant (P ≤ 0.01) increase in subjective lameness grades over the 2-week evaluation period, and hylan administration did not significantly (P ≤ 0.01) change the subjective lameness grade. Lameness induction caused significant (P ≤ 0.01) decrease in head and withers excursions during the lame forelimb support phase and significant (P ≤ 0.05) increase in head and withers excursions during the sound forelimb support phase. Synovitis induction was further characterized by significant (P ≤ 0.05) increases in total wbc, polymorphonuclear, and large and small mononuclear cell numbers, and synovial fluid total protein concentrations. Also, subjective scores for synovial sections were significantly (P ≤ 0.05) different from baseline values, but hylan treatment at the 1-, 2-, or 4-ml dose did not significantly (P ≤ 0.05) alter these variables, compared with baseline values or values in control horses. Hyaluronan concentrations were not altered by induction of synovitis or hylan treatment.

Although clinical use of hyaluronan for treatment of traumatic joint disease in horses is well accepted, the beneficial effect of hylan was not detectable in this study. Further studies are required to more fully characterize the possible beneficial effects of hyaluronan-based products for treatment of joint disease in equids.

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