Effects of pentoxifylline infusion on response of horses to in vivo challenge exposure with endotoxin.

Abstract: To evaluate the effect of pentoxifylline on response of horses to in vivo challenge exposure with endotoxin. Methods: 24 healthy horses in 3 treatment groups: pentoxifylline, endotoxin, or endotoxin and pentoxifylline. Methods: Horses of the pentoxifylline group were given a bolus of pentoxifylline (7.5 mg/kg of body weight, i.v.), followed by an infusion (3 mg/kg/h) over 3 hours, and those of the endotoxin group were given 20 ng of endotoxin/kg i.v. over 30 minutes. Those of the combination group were given both of the aforementioned compounds; pentoxifylline was administered immediately after endotoxin. Clinical (rectal temperature, heart and respiratory rates, blood pressure) and hematologic (WBC count; whole blood recalcification time; plasma fibrinogen, thromboxane B2, and 6-keto-prostaglandin F1 alpha concentrations; plasma plasminogen activator inhibitor activity; and serum tumor necrosis factor and interleukin 6 activities) variables were evaluated over 24 hours. Results: Compared with baseline values, there were no significant changes in any variable over time in the horses receiving only pentoxifylline, with the exception of a significant increase in WBC count. Rectal temperature, heart rate, mean blood pressure, WBC count, whole blood recalcification time, fibrinogen concentration, plasminogen activator inhibitor activity, tumor necrosis factor and interleukin 6 activities, and plasma thromboxane B2 concentration changed significantly over time in horses of the endotoxin and endotoxin-pentoxifylline combination groups. Respiratory rate and plasma 6-keto-prostaglandin F1 alpha concentration changed significantly over time only in horses of the endotoxin group. Compared with values for the endotoxin group, rectal temperature and respiratory rate were significantly lower, and whole blood recalcification time was longer for the endotoxin/pentoxifylline group. Conclusions: Beneficial effects of pentoxifylline are limited when it is administered i.v. to horses after in vivo challenge exposure with endotoxin.