Human small intestine is capable of restoring barrier function after short ischemic periods

Dirk H. S. M. Schellekens*, Inca H. R. Hundscheid, Claire A. J. I. Leenarts, Joep Grootjans, Kaatje Lenaerts, Wim A. Buurman, Cornelis H. C. Dejong, Joep P. M. Derikx

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Web of Science)

Abstract

AIM

To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR).

METHODS

In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker.

RESULTS

Plasma L/R ratio's were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 +/- 0.10 vs 0.20 +/- 0.09, P <0.05). At 120 min of reperfusion (120R), ratio's normalized (0.17 +/- 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P <0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR.

CONCLUSION

This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.

Original languageEnglish
Pages (from-to)8452-8464
Number of pages13
JournalWorld Journal of Gastroenterology
Volume23
Issue number48
DOIs
Publication statusPublished - 28 Dec 2017

Keywords

  • Intestinal ischemia-reperfusion
  • Intestinal barrier function
  • Intestinal permeability
  • Human
  • Dual-sugar absorption test
  • Tight Junctions
  • Citrulline
  • PLASMA CITRULLINE CONCENTRATION
  • MYELOABLATIVE THERAPY
  • PERMEABILITY
  • DISEASE
  • DAMAGE
  • TIGHT
  • INFLAMMATION
  • MARKER
  • INJURY
  • GUT

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