Published online Dec 28, 2017. doi: 10.3748/wjg.v23.i48.8452
Peer-review started: April 25, 2017
First decision: May 9, 2017
Revised: August 8, 2017
Accepted: August 15, 2017
Article in press: August 15, 2017
Published online: December 28, 2017
Processing time: 246 Days and 9.1 Hours
To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR).
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.
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.
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.
Core tip: Using an unique experiment human intestinal ischemia and reperfusion (IR) model, this is the first study to directly correlate histological data with intestinal permeability tests. The results reveal the ability of the intestine to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion. These results explain why there are often no signs of inflammation or bacterial translocation after short periods of intestinal ischemia. Exploration of the mechanisms responsible for this rapid recovery might impact understanding and treatment of intestinal diseases. Data from the dual-sugar absorption tests and citrulline reflect the histological perturbations during intestinal IR, highlighting the potential diagnostic value of these tests in patients with intestinal diseases associated with intestinal barrier loss.