Intestinal ischemia and reperfusion: beneficial effects of a platelet activating factor antagonist

Gut barrier dysfunction in conditions associated with intestinal ischemia and reperfusion (I/R) might contribute to the further development of multiple organ dysfunction. The present study evaluates the effects of platelet activating factor (PAF) antagonist in intestinal I/R injury.

Methods

Intestinal ischemia was induced by clamping of the superior mesenteric artery for 40 min followed by 12 h reperfusion. 15 min after the end of ischemia, the rats received intraperitoneal injections of saline or the PAF antagonist lexipafant (5 mg/kg), repeated after 6 h in the groups subjected to 12 h reperfusion. Myeloperoxidase (MPO) content in the small intestine, serum levels of interleukines-1 and 6, plasma protease inhibitors and intestinal endothelial and epithelial permeability were assesed.

Results

Intestinal I/R resulted in intestinal barrier dysfunction with pronounced plasma leakage to the intestinal lumen. A protely plasma activity was evident. MPO content significantly increased as did levels of interleukines. Treatment with the PAF inhibitor partly, though not fully, restored the changes caused by I/R.

Conclusion

PAF seems involved in the release of cytokines and consumption of protease inhibitors following intestinal I/R and the associated impairment of intestinal barrier integrity. Treatment with a PAF antagonist was effective in restoring changes caused by I/R, though not reaching normal levels.