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

Am J Vet Res. 1997 Nov;58(11):1291-9.

Abstract

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, i.v., 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / blood
  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Clonixin / analogs & derivatives*
  • Clonixin / pharmacology
  • Clonixin / therapeutic use
  • Disease Models, Animal
  • Drug Combinations
  • Endotoxemia / drug therapy
  • Endotoxemia / physiopathology
  • Endotoxemia / veterinary*
  • Escherichia coli
  • Escherichia coli Infections / blood
  • Escherichia coli Infections / veterinary
  • Hemodynamics / drug effects
  • Horse Diseases / blood
  • Horse Diseases / drug therapy*
  • Horse Diseases / physiopathology
  • Horses
  • Interleukin-6 / blood
  • Leukocyte Count / drug effects
  • Leukocyte Count / veterinary
  • Pentoxifylline / pharmacology
  • Pentoxifylline / therapeutic use*
  • Plasminogen Activator Inhibitor 1 / blood
  • Thromboxane B2 / blood
  • Time Factors
  • Tissue Plasminogen Activator / blood
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • flunixin meglumine
  • Tissue Plasminogen Activator
  • Pentoxifylline
  • Clonixin