Effect of a conjugate of polymyxin B-dextran 70 in horses with experimentally induced endotoxemia

Robert J. MacKay From the Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610 (MacKay, Clark) and Novartis Pharmaceuticals Corp, East Hanover, NJ 07936 (Logdberg, Lake).

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Carol K. Clark From the Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610 (MacKay, Clark) and Novartis Pharmaceuticals Corp, East Hanover, NJ 07936 (Logdberg, Lake).

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Lennart Logdberg From the Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610 (MacKay, Clark) and Novartis Pharmaceuticals Corp, East Hanover, NJ 07936 (Logdberg, Lake).

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Philip Lake From the Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610 (MacKay, Clark) and Novartis Pharmaceuticals Corp, East Hanover, NJ 07936 (Logdberg, Lake).

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Abstract

Objective

To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses.

Animals

15 horses during study 1 and 6 horses during study 2.

Procedures

3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCI) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lactate, and prostanoid concentrations. In study 2, horses were given ketoprofen (2.2 mg/kg) or saline solution 15 minutes before infusion of PBD. Fourteen days later, treatments were reversed, using a crossover design. Blood samples were obtained for measurement of thromboxane B2 (TXB2) concentration.

Results

For study 1, prior treatment with PBD completely blocked endotoxin-induced changes for heart and respiratory rates, rectal temperature, WBC count, and plasma tumor necrosis factor, interleukin 6, TXB2, and prostaglandin F1 concentrations. There was transient tachypnea, sweating, and increased plasma TXB2 concentration in horses given PBD (with or without LPS). Prior treatment with ketoprofen eliminated all PBD-induced signs and prevented the increase in plasma TXB2 concentration.

Conclusions

Signs of endotoxemia were prevented in horses by treatment with PBD, although its use was associated with mild adverse effects.

Clinical Relevance

When used in combination with a cyclooxygenase-inhibiting drug, PBD has potential for treatment of horses with endotoxemia. (Am J Vet Res 1999;60:68–75)

Abstract

Objective

To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses.

Animals

15 horses during study 1 and 6 horses during study 2.

Procedures

3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCI) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lactate, and prostanoid concentrations. In study 2, horses were given ketoprofen (2.2 mg/kg) or saline solution 15 minutes before infusion of PBD. Fourteen days later, treatments were reversed, using a crossover design. Blood samples were obtained for measurement of thromboxane B2 (TXB2) concentration.

Results

For study 1, prior treatment with PBD completely blocked endotoxin-induced changes for heart and respiratory rates, rectal temperature, WBC count, and plasma tumor necrosis factor, interleukin 6, TXB2, and prostaglandin F1 concentrations. There was transient tachypnea, sweating, and increased plasma TXB2 concentration in horses given PBD (with or without LPS). Prior treatment with ketoprofen eliminated all PBD-induced signs and prevented the increase in plasma TXB2 concentration.

Conclusions

Signs of endotoxemia were prevented in horses by treatment with PBD, although its use was associated with mild adverse effects.

Clinical Relevance

When used in combination with a cyclooxygenase-inhibiting drug, PBD has potential for treatment of horses with endotoxemia. (Am J Vet Res 1999;60:68–75)

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