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

Anne Baskett From the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Michelle Henry Barton From the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Natalie Norton From the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Brendan Anders From the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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James N. Moore From the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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SUMMARY

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 O55: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 TxB2, and 6-keto-PGF1 concentrations, pulse, rectal temperature, and attitude score. Pentoxifylline given before endotoxin resulted in significantly higher 6-keto-PGF1 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 TxB2 concentration, and 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group at 1 hour. In horses of the FM group, 6-keto-PGF1 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. (Am J Vet Res 1997;58:1291–1299)

SUMMARY

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 O55: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 TxB2, and 6-keto-PGF1 concentrations, pulse, rectal temperature, and attitude score. Pentoxifylline given before endotoxin resulted in significantly higher 6-keto-PGF1 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 TxB2 concentration, and 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group at 1 hour. In horses of the FM group, 6-keto-PGF1 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. (Am J Vet Res 1997;58:1291–1299)

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