Effect of pentoxifylline, flunixin meglumine, and their combination on a model of endotoxemia in horses

Objective-To compare effects of a single dose of pentoxifylline (PTX), flunixin meglumine (FM), and their combination (FM/PTX) in a model of equine endotoxemia. Animals-24 healthy horses, aged 2 to 15 years. Procedure-4 groups (n = 6/group) received 30 ng of Escherichia coli 055:B5 endotoxin/kg of body weight, IV, over 30 minutes, and 1 of the following preparations 15 minutes before and 8 hours after endotoxin infusion: FM, 1.1 mg/kg; PTX, 8 mg/kg; FM/ PTX, 1.1 mg of FM and 8 mg of PTX/kg; and saline solution bolus (ENDO). Clinical and hematologic variables were measured over 24 hours. Results-Compared with ENDO, FM given before endotoxin significantly reduced TxB(2), and 6-keto-PGF(1) concentrations, pulse, rectal temperature, and attitude score. Pentoxifylline given before endotoxin resulted in significantly higher 6-keto-PGF(1) concentration at 1.5 hours and significantly lower PAI-1 activity at 12 hours. Tumor necrosis factor and IL-6 activities in horses given PTX alone were not significantly different from values in those given the saline bolus. FM/PTX induced effects similar to those of FM alone on endotoxin-induced changes in temperature and TxB(2) concentration, and 6-keto-PGF(1) concentration was significantly lower than that in horses of the ENDO group at 1 hour. In horses of the FM group, 6-keto-PGF(1) concentration was significantly lower than that in horses of the ENDO group, from 0.5 hour to 2 hours. Horses of the FM and FM/PTX groups had significantly higher IL-6 activity at 1.5 and 2 hours than did horses of the PTX and ENDO groups; those of the FM and FM/PTX groups had significantly lower WBC count than did those of the PTX and ENDO groups. Conclusions-FM/PTX may help offset deleterious hemodynamic effects of endotoxin more effectively than does either FM or PTX alone.