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

Vanessa L. Cook Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Colleen T. Meyer Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Nigel B. Campbell Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Anthony T. Blikslager Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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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 B2 and prostaglandin E2 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 B2 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.

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 B2 and prostaglandin E2 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 B2 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.

Contributor Notes

Dr. Cook's present address is the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Supported by Merial Limited.

Dr. Cook was supported through a Morris Animal Foundation fellowship training award.

Dr. Meyer was supported by the Merck-Merial Veterinary Scholars Summer Research Program.

Dr. Meyer was a second-year veterinary student at the time of this study.

Presented in part at the 9th International Colic Symposium, Liverpool, England, June 2008.

The authors thank Dr. Jennifer Davis for assistance with interpretation of pharmacologic data and Jennifer Jones Shults and Marsha McDowell for assistance with collection of data.

Address correspondence to Dr. Cook.
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