Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum.

This research identifies the effects of ischemia and the drug flunixin on lipopolysaccharide (LPS) absorption in the jejunum tissue of horses. The findings show that ischemia increases LPS absorption, while flunixin delays recovery without increasing LPS absorption.

Research Methodology

• The study involved 12 horses. The horses were anesthetized, had a midline celiotomy performed, and the jejunum (a part of the small intestine) was located.
• Two sections (each 30 cm) of the jejunum, spaced 60 cm apart, were selected. One segment served as the control, while ischemia—loss of blood flow—was induced in the other segment for two hours.
• After the procedure, the horses were euthanized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin, a major nonsteroidal anti-inflammatory drug (NSAID) commonly used in veterinary medicine to reduce pain and inflammation.

Assessment Approaches

• The mucosal samples were analyzed in two different ways:
  • Tissues from six of the horses were used to assess permeability to radiolabeled LPS, providing a measure of how easily LPS penetrates the tissue.
  • The remaining six horses’ samples were incubated with fluorescent-labeled LPS (FITC-LPS) and then examined histologically, a microscopic study of tissue structure.
• Key indicators of mucosal response to LPS, notably production of Tumor Necrosis Factor-alpha (TNF-alpha) and LPS-binding protein (LBP), were also monitored.

Findings and Conclusions

• The results showed that ischemia significantly increased the mucosa’s permeability to LPS. However, after three hours, ischemic mucosa was not more permeable than the control tissue.
• The use of flunixin adversely affected the intestinal barrier function throughout the experiment, but it did not result in an increased mucosal permeability to LPS.
• Compared to control tissues, ischemia increased LPS-binding protein (LBP) production and LPS exposure reduced it. This suggests that the presence of ischemia prompts the tissue to produce more LBP, possibly as a defense mechanism.
• The researchers concluded that ischemia increased the passage of LPS across equine jejunal mucosa. While flunixin did delay mucosal recovery, it did not exacerbate LPS absorption. However, further in vivo investigations are required to determine the clinical implications of the flunixin-associated delayed mucosal recovery.