Epithelial ion transport in spring-lengthened jejunum in a porcine model.

Abstract

BACKGROUND AND AIM: Loss of functional small intestine in short bowel syndrome results in profound nutrient malabsorption and diarrhea. We previously developed an expandable spring device that triggers intestinal lengthening. The aim of this study was to assess the functional ion transport capabilities of spring-lengthened jejunum. METHOD: Mini-Yucatan pigs underwent laparotomy and spring placement in the jejunum. After 7 days, pigs were euthanized to retrieve spring-lengthened and distal control jejunum. Tissues were mounted in Ussing chambers to measure transepithelial resistance and short-circuit current (I). Forskolin and carbachol were used to measure cAMP- and calcium-mediated anion secretory capacities, and glucose was used for absorptive capacity. Tissue samples were then preserved for histopathology and immunochemistry. RESULTS: Intestinal segments exposed to springs became longer at euthanasia. Baseline transepithelial resistance and Iwere similar between spring-lengthened and control jejunum. Forskolin, carbachol, and glucose increased Iabove baseline in both lengthened and control jejunum. While glucose-stimulated Iwas similar between lengthened and control jejunum, forskolin- and carbachol-stimulated Iwere reduced. Spring-lengthened jejunum had greater mucosal area with deeper crypts and taller villi, but similar crypt: villus ratios as control jejunum. Spring-lengthened jejunum had thicker muscularis propria compared to controls. CONCLUSION: Spring-lengthening of small bowel does not disrupt mucosal barrier function, based on histological and functional assessments. While spring-lengthened jejunum showed reduced transepithelial secretory function, its absorptive function appears intact. This change may be related to early tissue remodeling during distraction enterogenesis and further investigation into the cellular changes induced by distraction enterogenesis are ongoing.