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

Objective-To determine the efficacy of polymyxin B-dextran 70 (PBD) for tre atment 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 giv en 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes . Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15 mi nutes 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 s amples 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 day s later, treatments were reversed, using a crossover design. Blood samples were obtained for measurement of thromboxane B-2 (TXB2) concentration. Results-For study 1, prior treatment with PBD completely blocked endotoxin- induced changes for heart and respiratory rates, rectal temperature, WBC co unt, and plasma tumor necrosis factor, interleukin 6, TXB2, and prostagland in F-1 concentrations. There was transient tachypnea, sweating, end increas ed plasma TXB2 concentration in horses given PBD (with or without LPS). Pri or treatment with ketoprofen eliminated ail 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-inhibitin g drug, PBD has potential for treatment of horses with endotoxemia.