Effects of flunixin meglumine on the recovery of ischaemic equine colonic mucosain vitro

Abstract

SummaryReasons for performing study: The effects of prostaglandins and nonsteroidal anti-inflammatory drugs (NSAIDs) on repair of equine intestinal mucosa are important since most horses with gastrointestinal diseases are routinely treated with NSAIDs, such as flunixin meglumine (FM), and these drugs can be toxic to equine gastrointestinal mucosa. Hypothesis: Flunixin meglumine would not affect recovery of equine colonic mucosa in vitro, 18 h after a reversible ischaemic injury. Methods: In 14 anaesthetised horses, a segment of pelvic flexure was subjected to 2 h of ischaemia and the horses were allowed to recover for 18 h. Seven horses received normal saline and 7 received FM, 1.1 mg/kg bwt i.v., at the end of ischaemia and 12 h later. Colonic mucosa was harvested during a second anaesthesia, 18 h after recovery from ischaemia and then horses were subjected to euthanasia. Transepithelial electrical resistance (TER) and transepithelial flux of tritiated mannitol were used to measure mucosal permeability during 4 h of incubation in Ussing chambers, with the following in vitro treatments: 1) no addition, 2) FM 14 mmol/l as powder, 3) FM 14 mmol/l in injectable form and 4) diluent for injectable FM. Histomorphological changes were assessed by light microscopy. Results: There were no significant differences in any of the measurements between saline and FM treated horses. The mucosal height of the ischaemic FM tissues incubated in diluent was significantly decreased compared to the nonischaemic tissues. Conclusions: Flunixin meglumine did not adversely affect barrier integrity in ischaemic equine colonic mucosa.evj_382 112..116

Effects of ischemia and reperfusion on production of nitrotyrosine, activation of eosinophils, and apoptosis in the large colonic mucosa of horses

“…The horses were donated for research purposes and were free of gastrointestinal tract diseases. These horses were involved in several overlapping studies [35][36][37][38] on ischemia and reperfusion that were performed with approval and under guidelines of the Institutional Animal Care and Use Committee of the University of Florida. Horses were fed grass hay (2% of body weight/d), and water was provided ad libitum.…”

The use of nonsteroidal anti‐inflammatory drugs in critically ill horses

“…Unfortunately, the study was statistically not powerful enough to make a conclusion on the difference in plasma LPS concentrations between flunixin meglumine and meloxicam‐treated horses . Additional experimental studies have also shown that flunixin meglumine does not retard recovery of barrier function in ischemic‐injured equine colon, at least at the level of the pelvic flexure . However, colonic LPS permeability was not assessed.…”

On the question of colic: Are answers beginning to emerge?

“…In recent years, much emphasis has been placed on the use of cyclo-oxygenase-independent [33] or COX-2 selective anti-inflammatory drugs to control this process, because there is laboratory evidence to suggest that the older, nonselective nonsteroidal anti-inflammatory drugs, such as flunixin, may inhibit mucosal barrier healing [34]. However, the available data are conflicting, and a recent study has shown no detrimental effect of flunixin on ischaemic equine colonic bs_bs_banner Equine Veterinary Journal ISSN 0425-1644 DOI: 10.1111/j.2042-3306.2012.00593.x mucosa [35], leading the authors to question the current emphasis on COX-2 selective drugs. Clinicians should be cautious about extrapolating in vitro findings straight into clinical practice, and large-scale, prospective, randomised clinical trials are needed to resolve the dilemma over the potential advantages of COX-2 selective drugs over other nonsteroidal anti-inflammatory drugs, particularly as their use can add considerably to the cost of post operative care.…”