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Intestinal Permeability for Macromolecules Following Mechanical Ileus in Mice
Xue Zhao, Till Macheroux, Michael S. Kasparek, Mario H. Mueller, Martin E. Kreis* Surgery, University of Munich, Munich, Germany
Introduction: Acute mechanical ileus is a frequent disorder seen in general surgery which - if untreated - terminates in peritonitis secondary bacterial translocation. We aimed to investigate the time course of changes in gut permeability during acute mechanical ileus for molecules of different molecular weight. Methods: C57Bl6 mice were anesthetized by isoflurane inhalation and gavaged with flourescein isothiocyanate conjugated dextrane (FITC-dextrane, 4.4 kDa) and horseradish peroxidase (HRP, 40 kDa). After a mini- laparotomy, the small intestine was ligated approximately 5 cm distal to the ligament of Treitz, while controls received a mini-laparotomy only. Intestinal permeability was assessed in ileus animals or controls 3 and 9 hours later in different subgroups (each n=4). 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: At 3 hours after the beginning of mechanical ileus, the FITC-dextrane concentration was 187±7.6 ng/ml in ileus animals and 147±8.1 ng/ml in sham controls (p<0.05), while it was 86±8.9 and 62±0.8 ng/ml at the 9 hour time point (p<0.05). For the bigger molecule, HRP, concentrations at 3 hours were 5.6±3.6 ng/ml in ileus animals and 4.1±1.6 ng/ml in sham controls which was not different. At 9 hours the serum concentrations were 23.0±4.3 ng/ml in ileus animals which was higher compared to 9.0±3.1 ng/ml in sham controls (p<0.05). Conclusions: Intestinal permeability for macromolecules increases a few hours after acute mechanical ileus. It seems that soon after the beginning of mechanical ileus, intestinal permeability is increased for small-sized molecules, while it takes a few hours more until it is also increased for bigger sized molecules.
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