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Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum

Dianne Little BVSc, PhD1,2, S. Aubrey Brown BS3,4, Nigel B. Campbell BVetMed, PhD5,6, Adam J. Moeser PhD7,8, Jennifer L. Davis DVM, PhD9,10, and Anthony T. Blikslager DVM, PhD11,12
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  • 1 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 3 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 4 Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 5 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 6 Departments of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 7 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 8 Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 9 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 10 Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 11 Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 12 Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

Objective—To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.

Animals—18 horses.

Procedures—Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.

Results—Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flu-nixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cy-clooxygenase-independent effects.

Conclusions and Clinical Relevance—Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.

Abstract

Objective—To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.

Animals—18 horses.

Procedures—Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.

Results—Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flu-nixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cy-clooxygenase-independent effects.

Conclusions and Clinical Relevance—Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.

Contributor Notes

Supported by the American Quarter Horse Association. Ms. Brown was supported by the Merck-Merial Summer Internship program at the College of Veterinary Medicine, North Carolina State University.

Address correspondence to Dr. Blikslager.