Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia

Abstract

Objective - To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion. Animals - 24 horses. Procedure - Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, IV, q 12 h), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or etodolac (23 mg/kg, IV, 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 and Clinical Relevance - 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.