ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Pediatric Surgery
In Vitro Study of Spontaneous Motility and Cholinergic Responses in the Human Hirschsprung's Disease Colon
Provisionally accepted
- 1Oscar Langendorff Institute of Physiology, University Hospital Rostock, Rostock, Germany
- 2Department of paediatric surgery, University Hospital Rostock, Rostock, Germany
- 3Center of Transdisciplinary Neurosciences Rostock (CTNR), Rostock, Germany
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Abstract Background: The current standard treatment of Hirschsprung's disease (HD) involves complete resection of the aganglionic intestinal segment with routine rectal irrigation pre-and postoperatively. To date, our understanding of the underlying pathomechanisms is not sufficient to warrant modifying this therapeutic approach. Here, we utilized resected tissue specimens from children with HD to investigate spontaneous motility and cholinergic responses in circular muscle from both ganglionic and aganglionic colon in vitro. Methods: Full-thickness intestinal samples (from both aganglionic and ganglionic segments) were obtained intraoperatively from children with HD undergoing pull-through surgery. After removing the mucosal tissue and longitudinal smooth muscle, we prepared specimens consisting of circular muscle layer and submucosal tissue. These deafferentiated specimens were mounted in the organ bath to record isometric forces during spontaneous motility or following cholinergic stimulation. Results: Regarding spontaneous motility, the basal tone was observed in all specimens, and phasic contractions were observed in 81% versus 63% of ganglionic and aganglionic specimens, respectively. Both basal tone and phasic contractions were abolished in the presence of 40 mM EDTA indicating Ca2+ dependence, yet atropine (1 µM) had no effect on these measures. Increasing concentrations of the muscarinic receptor agonist carbachol raised the basal tone of ganglionic specimens, but significantly less potently in aganglionic tissue. In contrast, carbachol-evoked phasic contractions were still observed and even larger in aganglionic specimens than in ganglionic tissue. Conclusions: We conclude that the circular muscle of aganglionic colonic segments retains the ability to establish a Ca2+-dependent and atropine-insensitive spontaneous motility similar to the circular muscle of ganglionic tissue. However, both tissue segments differed considerably in response to external cholinergic stimulation with significantly enhanced phasic-to-tonic contraction ratios in aganglionic specimens. These findings will help understand the persistent circular muscle contraction in aganglionic bowel which is still a major challenge in the preoperative HD management.
Keywords: Hirschsprung Disease, organ bath, Carbachol, Atropine, contractility, Colon, Aganglionosis
Received: 03 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Schulze, Lindert, Köhling, Märzheuser and Kirschstein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Felix Schulze, felix.schulze@med.uni-rostock.de
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