Resection-induced intestinal adaptation and the role of
enteric smooth muscle
☆
Colin A. Martin
a
, Kathryn Q. Bernabe
b
, Janice A. Taylor
a
, Rajalakshmi Nair
a
,
Richard J. Paul
c
, Jun Guo
a
, Christopher R. Erwin
a
, Brad W. Warner
a,
⁎
a
Division of Pediatric General and Thoracic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center,
University of Cincinnati College of Medicine, Cincinnati, OH 45729, USA
b
Ochsner Clinic Foundation, Department of Surgery, New Orleans, LA 70121, USA
c
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Received 29 January 2008; accepted 8 February 2008
Key words:
Intestinal resection;
Adaptation;
Enteric smooth muscle;
Epidermal growth
factor receptor;
Hyperplasia;
Intestinal contractility
Abstract
Background: Intestinal adaptation after massive small bowel resection (SBR) involves all layers of the
bowel wall. Most prior work has focused on changes that occur in the intestinal mucosa. However, the
contribution of the underlying intestinal smooth muscle (ISM) to the overall adaptation response
remains unclear.
Methods: Male C57BL/6 or waved-2 (diminished activity of the epidermal growth factor receptor) mice
underwent a 50% proximal SBR or sham operation, and the remnant ileum was harvested 3, 7, and 28
days. Markers of adaptation (villus height, bowel length, circumference, and ISM thickness) and ISM
proliferation were recorded. Contractility was measured by attaching the distal ileum to strain gauge
transducers and exposed to varying doses of carbachol.
Results: Intestinal smooth muscle thickness was unchanged at any given time-point after resection;
however, the bowel caliber and length were increased, and augmented rates of ISM proliferation were
identified. Contractility was increased at 7 days after SBR. Waved-2 mice demonstrated minimal
proliferation or intestinal lengthening in response to SBR.
Conclusion: Compared with resection-induced thickening of the mucosa, proliferative changes in the
ISM are unique and primarily affect bowel caliber, length, and contractility. Epidermal growth factor
receptor signaling appears to play a significant role in adaptation of the ISM cellular compartment.
© 2008 Elsevier Inc. All rights reserved.
Short gut syndrome (SGS) after massive intestinal loss
caused by neonatal necrotizing enterocolitis, intestinal
atresia, or midgut volvulus is a major cause of morbidity
and mortality for children. Optimizing the compensatory
adaptive response in the intestine that follows massive small
bowel resection (SBR) is one important approach in treating
SGS. The bulk of prior studies have necessarily focused on
understanding resection-induced adaptation in the intestinal
mucosa. Indeed, morphological changes are readily apparent
www.elsevier.com/locate/jpedsurg
Presented at the 59th Annual Meeting of the Section on Surgery, American
Academy of Pediatrics, San Francisco, CA, October 25-27, 2007.
☆
Supported by National Institutes of Health: RO1 DK53234, (BWW),
and Digestive Disease Research Development Core Center of Cincinnati—
R24 DK064403.
⁎
Corresponding author. Division of Pediatric Surgery, St Louis
Children's Hospital, One Children's Place Suite 5560, St. Louis, MO
63110, USA. Tel.: +1 314 454 6022; fax: +1 314 454 2442.
E-mail address: brad.warner@wustl.edu (B.W. Warner).
0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.jpedsurg.2008.02.015
Journal of Pediatric Surgery (2008) 43, 1011–1017