Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.788614
Title: Jejunoileal absorption of simple nutrients in a canine model of small bowel autotransplantation
Author: Walters, Anne Marisia
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1994
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Abstract:
Since 1988, more than 50 patients world-wide have received small bowel allografts, yet very little is known about the absorptive capabilities of transplanted small bowel. Background: Transplantation of an organ requires the transection of all nerves and lymphatics connecting that organ to the donor. The effect this has on jejunal and ileal absorptive function is poorly documented and ambiguous. This study specifically addresses this question. Transplantation: Transference of an organ from donor to recipient involves several steps, each of which may potentially damage the graft; this could result in impaired absorptive function in a small bowel allograft. (a) Organ procurement: the organ is flushed and cooled with preservation solution, allowing storage. (b) Ischaemic time: from flushing of the graft with the cold preservation solution until circulation is restored in the recipient. (c) Reperfiision: when the transplanted organ is revascularised with recipient's blood. (d) Immunosuppression : pharmacological agents which dampen down the recipient's immune response are required to prevent graft rejection; e.g. cyclosporine A affects absorption. (e) Rejection: the high content of lymphoid tissue renders small bowel highly immunogenic. Acute rejection targets the mucosa, potentially affecting absorption from its onset. Aim of Study: This model of small bowel autotransplantation assesses, in isolation, the effect of denervation and lymiphatic transection on small bowel absorption. It excludes the confounding factors of transplantation injury just described. This is crucial for three reasons: 1. To assess any alterations in the physiology of absorption caused by denervation and lymphatic transection by using simple electrolyte and single nutrient solutions, with documented absorptive pathways. 2. Only after the effect of denervation and lymphatic transection has been clearly documented, can meaningful experiments on the absorptive capability of small bowel transplants be carried out, with a view to assessing the effect of transplantation injury. 3. Major absorptive defects in autotransplanted small bowel would imply their existence in transplanted small bowel, which may render it unsuitable to provide adequate nutrition in patients. This model of small bowel autotransplantation examines the absorption of a member of each of the major nutritional groups, allowing assessment of a broad spectrum of absorptive pathways. Glucose, glycine, phenylalanine, and oleic acid (a long chain fatty acid), were each studied separately, as single nutrient solutions. Canine Model of jejunoileal Autotransplantation: This model represents a jejunoileum which is extrinsically denervated, with no connection of the intrinsic neural pathways to proximal or distal gut, and with total lymphatic interruption. Each dog had an 80cm isolated loop of jejunum or ileum with a perfusion cannula at the proximal end, and a distal stoma. Two control groups were created to match the two autotransplanted groups; these control animals did not undergo the model of autotransplantation, but simply had the 80cm loop of jejunum or ileum created. The four groups were: Group 1 - control jejunum Group 2 - autotransplanted jejunum Group 3 - control ileum Group 4 - autotransplanted ileum. Design and Conduct of Study: The four groups of dogs, each containing a minimum of six animals, were studied at an early phase post-operatively (Week 1 and Week 2), and had the experiments repeated at a later phase (Week 8 and Week 9). Each of the five isotonic test solutions used polyethylene glycol as a non-absorbable marker to determine steady-state conditions. Each was perfused at a rate of 3ml/min at 38°C for three hours, being repeated on a further two occasions, resulting in triplicate experiments at both early and late study points. Loop effluent was analysed for volume, sodium, chloride, potassium, and for the glucose, amino acid or oleic acid content. Transit time was also measured. This provided over 23,000 samples for analysis. Summary of Results: Denervation and lymphatic transection were found to have little or no adverse effect on absorption of electrolytes or simple nutrients from the jejunum or ileum Absorption of volume, sodium, and chloride was not significantly altered after autotransplantation of the jejunum or the ileum, nor was absorption of glucose or oleic acid. Glycine and phenylalanine absorption were marginally reduced only in autotransplanted ileum at both early and late time points. Potassium secretion was unaffected, with the solitary exception of the oleic acid solution in the ileum, where it was increased in autotransplants. Transit time was significantly slower in autotransplanted jejunum, but not in autotransplanted ileum. Conclusion: This study has provided essential physiological background data on absorption from both normal and denervated small bowel. It forms the solid foundation of basic knowledge required to allow further meaningful investigation of the effect of transplantation on small bowel absorption. Only now, with the basic effects of lymphatic transection and denervation clearly documented, can further studies be conducted to assess the effect which the several different components of transplantation injury may have on absorption. There is clearly no physiological reason for transplanted small bowel to have a major absorptive defect, which is encouraging for the future of clinical small bowel transplantation. As no specific nutrient out of the wide range assessed showed major impairment of absorption, it should permit small bowel transplant patients to be able to enjoy a normal unrestricted diet. If transplantation injury causes no permanent damage to a small bowel graft, and rejection can be controlled, then absorption from the transplanted bowel should be sufficient to sustain life.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.788614  DOI: Not available
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