Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum.
OBJECTIVE
To determine whether ischemia and flunixin affect in vitro lipopolysaccharide (LPS) absorption in samples of the jejunum of horses.


METHODS
12 horses.


METHODS
Horses were anesthetized, a midline celiotomy was performed, and the jejunum was located. Two 30-cm sections of jejunum (60 cm apart) were selected. One segment was designated as control tissue; ischemia was induced in the other segment for 120 minutes. Horses were then euthanatized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin. Tissues from 6 horses were used to assess permeability to radiolabeled LPS; mucosal samples from the remaining 6 horses were incubated with fluorescent-labeled LPS (FITC-LPS) and examined histologically. Production of tumor necrosis factor-alpha (TNF-alpha) and production of LPS-binding protein (LBP) were assessed as indicators of mucosal response to LPS.


RESULTS
Ischemia significantly increased mucosal permeability to LPS, but by 180 minutes, the mucosa was not more permeable than control tissue. Flunixin treatment adversely affected intestinal barrier function throughout the experiment but did not result in increased mucosal permeability to LPS. Compared with control tissues, LBP production was increased by ischemia and reduced by exposure to LPS. In ischemic tissue, FITC-LPS entered the lamina propria but TNF-alpha was produced on the mucosal side only, indicating little response to the absorbed LPS.


CONCLUSIONS
Ischemia increased LPS passage across equine jejunal mucosa. Flunixin delayed mucosal recovery but did not exacerbate LPS absorption. Evaluation of the clinical importance of flunixin-associated delayed mucosal recovery requires further in vivo investigation.
Tomlinson
Julia E
JE
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Blikslager
Anthony T
AT
D000209:Acute-Phase Proteins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western / Q000662:veterinary; D002352:Carrier Proteins / Q000378:metabolism; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D005453:Fluorescence; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism / Q000662:veterinary*; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D003002:Clonixin; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C014557:flunixin