Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum

Am J Vet Res. 2009 Aug;70(8):992-1000. doi: 10.2460/ajvr.70.8.992.

Abstract

Objective: To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia.

Animals: 18 horses.

Procedures: Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B(2) and prostaglandin E(2) metabolite (PGEM) concentrations were determined.

Results: Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B(2) concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery.

Conclusions and clinical relevance: Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury.

Publication types

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

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / therapeutic use
  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Blotting, Western / veterinary
  • Clonixin / analogs & derivatives*
  • Clonixin / therapeutic use
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Eicosanoids / blood
  • Electrophoresis, Polyacrylamide Gel / veterinary
  • Horse Diseases / drug therapy*
  • Horses
  • Ischemia / drug therapy
  • Ischemia / veterinary*
  • Jejunal Diseases / drug therapy
  • Jejunal Diseases / veterinary*
  • Sulfones / therapeutic use*
  • Thromboxane B2 / blood

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Eicosanoids
  • Sulfones
  • Thromboxane B2
  • flunixin meglumine
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • 4-Butyrolactone
  • Clonixin
  • firocoxib