Time-Dependent Alterations of Gut Wall Integrity in Small Bowel Obstruction in Mice

Abstract

Background: Small bowel obstruction (SBO) is one of the most common disorders in surgical emergency departments. Without resolution of the obstructed bowel segments, patients may develop multiorgan failure. The aim of this study was to investigate whether morphological damage of the intestinal wall during SBO may lead to molecular translocation and how this may impair intestinal motility.

Methods: C57Bl6 mice were laparotomized, and the small intestine was ligated 5 cm oral to the coecum for SBO. Controls received minilaparotomy only. Animals were sacrificed 3 h, 9 h, and 24 h after SBO. Morphological changes were evaluated on hematoxylin and eosin histology by a standardized score. Intestinal motility was determined by recording intraluminal pressure of the small intestine in vitro. Permeability was measured by fluorospectroscopy and ELISA of blood samples after oral gavage with fluorescein isothiocyanate (FITC)-dextrane and horse radish peroxidase. Data are mean ± SD.

Results: Three hours after SBO, FITC-dextrane uptake was increased to 187.6 ± 15.2 ng/mL compared to controls (P = 0.011). At 9 h, uptake of horse radish peroxidase (23.0 ± 8.6 ng/mL, 9.0 ± 6.3 ng/mL, P = 0.039) and FITC-dextrane (86.8 ± 17.8 ng/mL, 62.0 ± 1.6 ng/mL, P = 0.029) was higher compared to controls. Motility was increased to 162.2 ± 20.2 area under the curve (AUC) compared to 121.3 ± 20.3 AUC in controls, P = 0.009 and an increased histology score was observed at 9 h (3.2 ± 1.8 versus 0.6 ± 0.7, P = 0.003). Twenty-four hours after SBO, histology score was 3.8 ± 1.7, which was higher than 0.9 ± 0.7 in controls (P = 0.001). Intestinal motility was decreased 24 h after SBO compared to sham controls (146.0 ± 21.4 AUC versus 198.9 ± 21.2 AUC, P = 0.003).

Conclusions: SBO entails a time dependent epithelial damage to the mucosa. In parallel, molecular changes in the gut mucosal barrier occur as early as 3 h after the onset of SBO with a subsequent increase in permeability. Initial intestinal hypermotility is followed by a decrease in motility.

Keywords: Gut wall integrity; Mechanical ileus; Motility; Permeability; SBO; Small bowel obstruction.