EFFECTS OF PENTOXIFYLLINE INFUSION ON RESPONSE OF HORSES TO IN-VIVO CHALLENGE EXPOSURE WITH ENDOTOXIN

Objective-To evaluate the effect of pentoxifylline on response of hors es to in vivo challenge exposure with endotoxin. Animals-24 healthy ho rses in 3 treatment groups: pentoxifylline, endotoxin, or endotoxin an d pentoxifylline line. Procedure-Horses of the pentoxifylline group we re given a bolus of pentoxifylline (7.5 mg/kg of body weight, IV), fol lowed by an infusion (3 mg/kg/h) over 3 hours, and those of the endoto xin group were given 20 ng of endotoxin/kg IV over 30 minutes. Those o f the combination group were given both of the aforementioned compound s; pentoxifylline was administered immediately after endotoxin. Clinic al (rectal temperature, heart and respiratory rates, blood pressure) a nd hematologic (WBC count; whole blood recalcification time; plasma fi brinogen, thromboxane B-2, and 6-keto-prostaglandin F1(alpha) concentr ations; plasma plasminogen activator inhibitor activity; and serum tum or necrosis factor and interleukin 6 activities) variables were evalua ted over 24 hours. Results-Compared with baseline values, there were n o significant changes in any variable over time in the horses receivin g only pentoxifylline, with the exception of a significant increase in WBC count. Rectal temperature, heart rate, mean blood pressure, WBC c ount, whole blood recalcification time, fibrinogen concentration, plas minogen activator inhibitor activity, tumor necrosis factor and interl eukin 6 activities, and plasma thromhoxane B-2 concentration changed s ignificantly over time in horses of the endotoxin and endotoxin-pentox ifylline combination groups. Respiratory rate and plasma 6-keto-prosta glandin F1(alpha) concentration changed significantly over time only i n horses of the endotoxin group. Compared with values for the endotoxi n group, rectal temperature and respiratory rate were significantly lo wer, and whole blood recalcification time was longer for the endotoxin /pentoxifylline group. Conclusion-Beneficial effects of pentoxifylline are limited when it is administered IV to horses after in vivo challe nge exposure with endotoxin.