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Intestinal Permeability Is Increased During Postoperative Ileus in Mice
Xue Zhao2, Till M. Macheroux2, Michael S. Kasparek2, Mario Mueller2,3, Martin E. Kreis*1
1Surgery (CBF), Charité University Medicine, Berlin, Germany; 2Surgery, University of Munich, Munich, Germany; 3Gastroenterology, University of Zuerich, Zuerich, Switzerland

Introduction: Pathophysiology of postoperative ileus (POI) involves an intestinal inflammatory response. One potential mechanism is translocation of macromolecules from the gut lumen. We aimed to investigate whether the time course of translocation is dependent on molecular weight.
Methods: C57Bl6 mice were deeply anesthetized by isoflurane inhalation and gavaged with flourescein isothiocyanate conjugated dextrane (FITC-dextrane, 4.4 kDa) and horseradish peroxidase (HRP, 40 kDa). One hour later, a mini-laparotomy was performed and the small intestine manipulated in standardized fashion to induce POI, while control animals received sham laparotomy without manipulation. Intestinal permeability was assessed in POI animals or sham controls 1, 3 and 9 hours later in different subgroups (each n=6). For this purpose blood was taken by right ventricular puncture and serum concentrations of FITC-dextrane and HRP determined by spectrophotometry. Data are mean±SEM.
Results:
Serum levels of FITC-dextrane (4.4 kDa) in ng/ml; *p<0.05; **p<0.001 POI vs. sham
Sham 72 ± 5 83 ± 2 56 ± 6 (1h / 3h / 9h)
POI 120 ± 8* 183 ± 22** 65 ± 5 (1h / 3h / 9h)
Serum levels of horse radish peroxidase (40 kDa) in ng/ml; *p<0.05 POI vs. sham.
Sham 198 ± 18 240 ± 29 226 ± 24 (1h / 3h / 9h)
POI 350 ± 38* 388 ± 38* 300 ± 28 (1h / 3h / 9h)
Conclusions: Intestinal permeability for macromolecules was already increased a few hours after induction of postoperative ileus. This appeared to be independent of their molecular weight. Translocation of macromolcules into the intestinal wall early after induction of postoperaitve ileus is a potential trigger of subsequet intestinal inflammatory responses.
Supported by the Else Kröner-Fresenius Stiftung 2011_A214.


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