Enteric Physiology of the Transplanted Gut: Absorption and Motility

Sarr, Michael G.

doi:10.1159/000172427

Cited by 8 publications

(10 citation statements)

References 56 publications

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“…1 Unlike the heart, lung, kidney, and liver, which function quite well despite the complete organ isolation and the obligate denervation necessitated by the transplantation procedure, small intestinal function is modulated extensively by extrinsic and enteric neural input. [2][3][4][5] The study of these aspects of gut dysfunction after transplantation in animal models will help us to understand the underlying mechanisms mediating the enteric dysfunction of transplantation.…”

Section: Introductionmentioning

confidence: 99%

Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Fatima

Houghton

Sarr

2007

Journal of Gastrointestinal Surgery

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Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT.

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Section: Introductionmentioning

confidence: 99%

Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Fatima

Houghton

Sarr

2007

Journal of Gastrointestinal Surgery

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“…Therefore, the secretion and absorption function of intestinal graft is one of the most important factors for successful intestinal transplantation. The studies have demonstrated that intestinal absorptive function has been impaired following small intestinal transplantation [5], [6], and the defects in intestinal absorptive function occur even in nonrejecting small intestinal grafts [7], [8]. However, intestinal secretion function after intestinal transplantation is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice

Song

Liu

et al. 2013

PLoS ONE

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The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3 - and Cl- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3 - and Cl- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3 - and Cl- secretions in mice, but forskolin-stimulated HCO3 - and Cl- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα.

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“…The surgical technique leads to extrinsic denervation, disruption of intrinsic neural continuity, and lymphatic transection. There is evidence that after small-bowel transplantation (SBTx) fasting motility is controlled by the intrinsic nervous system, but is temporally dissociated with that of the native intestinal remnant [28]. Extrinsic sympathetic re-innervation can occur partially during the first year after transplantation, but its efficacy on motility control is expected to be poor [20].…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, the lymphatic vessels can regenerate within a few weeks after transplantation without major improvement in absorption. Moreover, it has been demonstrated that circulating hormones do not alter temporal coordination of intestinal motor patterns [28].…”

Section: Introductionmentioning

confidence: 99%

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

et al. 2003

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In this study we assessed functional changes (motility and absorption) of intestinal allografts in a large-animal model of orthotopic small bowel transplantation in swine. Studies were performed on non-rejecting animals in the early and late stages after transplantation and after induction of different grades of acute rejection. Immunosuppression consisted of oral FK506 and mycophenolate mofetil. In each study group we regulated drug administration, in terms of dosage and timing, in order to induce different grades of acute rejection or to prevent it. Migrating myoelectrical complexes were recorded in fasting animals so that motility could be assessed. Mucosal biopsy of the allograft and D-xylose absorption tests were performed on the same day as the motility study. In the early stages following intestinal transplantation, we observed in non-rejecting animals a slightly increased graft motility and a marked carbohydrate malabsorption. Recovery of the carbohydrate absorption capacity occurs within 2 months, but the persistence of diarrhea leads to partial malabsorption and to a lack of normal weight gain. Motility reduction correlates with the grade of acute rejection and becomes significant at a later stage, when rejection is severe. Allograft carbohydrate absorption, on the contrary, is markedly reduced in all rejecting pigs, irrespective of the grade of rejection. In summary, the early functional impairment of non-rejecting animals has multifactorial causes due to surgery and immunosuppression (drug toxicity), and its occurrence suggests the need for specific guidelines for clinical early postoperative enteral feeding. The functional studies adopted here are helpful in defining the grade of functional impairment with or without acute rejection; however, they are not useful for early detection of ongoing acute rejection of the small bowel graft.

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Enteric Physiology of the Transplanted Gut: Absorption and Motility

Cited by 8 publications

References 56 publications

Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

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