Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia.
OBJECTIVE
To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion.


METHODS
24 horses.


METHODS
Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, i.v., q 12 h), flunixin meglumine (1.1 mg/kg, i.v., q 12 h), or etodolac (23 mg/kg, i.v., q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithelial flux of tritium-labeled mannitol measured mucosal permeability. Denuded villous surface area and mean epithelial neutrophil count per mm2 were calculated. Western blot analysis for cyclooxygenase (COX)-1 and -2 was performed. Pharmacokinetics of flunixin and etodolac and eicosanoid concentrations were determined.


RESULTS
Ischemic-injured tissue from horses treated with flunixin and etodolac had significantly lower TER and increased permeability to mannitol, compared with that from horses treated with saline solution. Epithelial denudation after ischemia and 18 hours after recovery was not significantly different among treatments. Both COX-1 and -2 were expressed in ischemic-injured and nonischemic tissues. Ischemia caused significant upregulation of both COX isoforms. Eicosanoid concentrations were significantly lower in tissues from flunixin and etodolac-treated horses, compared with that from horses treated with saline solution.


CONCLUSIONS
Flunixin and etodolac treatment retarded recovery of intestinal barrier function in jejunal mucosa after 18 hours of reperfusion, whereas tissues from horses treated with saline solution recovered baseline values of TER and permeability to mannitol.
Tomlinson
Julia E
JE
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Wilder
B Osbone
BO
Young
Karen M
KM
Blikslager
Anthony T
AT
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D003002:Clonixin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015777:Eicosanoids / Q000378:metabolism; D017097:Electric Impedance; D004848:Epithelium / Q000098:blood supply; D017308:Etodolac / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015870:Gene Expression; D006652:Histological Techniques; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007511:Ischemia / Q000188:drug therapy / Q000662:veterinary*; D007527:Isoenzymes / Q000378:metabolism; D007583:Jejunum / Q000098:blood supply*; D008353:Mannitol; D009504:Neutrophils; D010147:Pain Measurement / Q000662:veterinary; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015424:Reperfusion / Q000662:veterinary; D013997:Time Factors; D014316:Tritium
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007527:Isoenzymes; D014316:Tritium; D017308:Etodolac; D008353:Mannitol; C014558:flunixin meglumine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003002:Clonixin