IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2012;4(4):219-227

Original Article
Novel method for studying postoperative ileus in mice

Sjoerd HW van Bree, Andrea Nemethova, Fleur S van de Bovenkamp, Pedro Gomez-Pinilla, L Elbers,
Martina Di Giovangiulio, Gianluca Matteoli, Jan van der Vliet, Cathy Cailotto, Michael WT Tanck, Guy EE

Tytgat institute of Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic
Medical Center, Amsterdam, the Netherlands; Department of Clinical and Experimental Medicine, Translational
Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium; Department of
Biostatistics, Academic Medical Center, Amsterdam, the Netherlands

Received September 23, 2012; Accepted November 15, 2012; Epub December 26, 2012; Published December
31, 2012

Abstract: Introduction: Postoperative ileus (POI) is characterized by a transient inhibition of coordinated motility of
the gastrointestinal (GI) tract after abdominal surgery and leads to increased morbidity and prolonged hospitalization.
Currently, intestinal manipulation of the intestine is widely used as a preclinical model of POI. The technique
used to manipulate the intestine is however highly variable and difficult to standardize, leading to large variations
and inconsistent findings between different investigators. Therefore, we developed a device by which a fixed and
adjustable pressure can be applied during intestinal manipulation. Methods: The standardized pressure manipulation
method was developed using the purpose-designed device (Figure 1D). First, the effect of graded manipulation
was examined on postoperative GI transit. Next, this new technique was compared to the conventional manipulation
technique used in previous studies. GI transit was measured by evaluating the intestinal distribution of orally
gavaged fluorescein isothiocyanate (FITC)-labeled dextran. Infiltration of myeloperoxidase positive cells and cytokine
production (ELISA) in the muscularis externa of the intestine were assessed. Results: Increasing pressures resulted
in a graded reduction of intestinal transit and was associated with intestinal inflammation as demonstrated by influx
of leukocytes and increased levels of IL-6, IL-1β and MCP-1 compared to control mice. With an applied pressure of 9
grams a similar delay in intestinal transit could be obtained with a smaller standard deviation, leading to a reduced
intra-individual variation. Conclusions: This method provides a reproducible model with small variation to study the
pathophysiology of POI and to evaluate new anti-inflammatory strategies. (IJPPP1209001).

Keywords: Gastrointestinal motility and physiology, intestinal transit, mice, postoperative ileus, inflammation

Address all correspondence to:
Dr. Sjoerd van Bree
Tytgat Institute for Liver and Intestinal Research
Academic Medical Centre, University of Amsterdam
Meibergdreef 69-7, 1105 BK
Amsterdam, The Netherlands.
Phone: +31-20-5665948; Fax: +31-20-5669190
E-mail: s.h.vanbree@amc.uva.nl