Contractility Assessment of Gut Tissues from Hirschsprung and Primary PIPO: A Pilot Study

Background: Primary chronic intestinal pseudo-obstructions and Hirschsprung disease are rare genetic diseases recognized as severe intestinal dysmotility pathologies.These monogenic disorders, with prenatal or neonatal onset in the most severe forms, are characterized by gut contraction impairments, which lead to recurrent intestinal pseudo-obstructions.The aim of this pilot work is to quantify the contraction ability of ex-vivo gut tissues affected with these pathologies.Methods: A dynamometric system was implemented ex-novo to measure changes in the force and displacement exerted by intestinal samples during contraction pharmacologically induced with carbachol.Contractile properties were assessed in human intestinal tissues collected from pediatric/ young adult patients diagnosed with genetic primary chronic intestinal pseudo-obstruction or Hirschsprung disease.The control group consisted of patients with intestinal diseases other than primary chronic intestinal pseudo-obstruction and Hirschsprung disease, who had neved had intestinal contraction problems.To assess the homogeneity of the control population different parameters (sex, age, tissue preservation and intestinal tract) were evaluated.Based on these results, comparisons between case and control populations were performed.Results: Gut muscles from pediatric controls exert similar forces independently of age, sex, intestinal tract (either colon or ileum) and preservation mode.The main outcome demonstrated that gut muscles from patients affected with genetic primary chronic intestinal pseudo-obstruction and Hirschsprung disease display significantly reduced contractile activity compared with controls.Conclusions: This study aims to improve knowledge of these diseases, providing quantitative data about intestinal smooth muscle contraction.In perspective, this approach might be exploited to support the screening of promising therapeutic molecules.