Because of the expense, potential complications and inconvenience of long-term parenteral nutrition, there has been an interest in surgical therapy for the short bowel syndrome. Functional intestinal mucosa called neomucosa will grow over intestinal defects patched with a variety of materials. However, it is not clear that sufficient neomucosa can be produced to significantly increase nutrient absorption because of a slow rate of growth and marked contraction of the patched defect. The purpose of this study is to determine if the quantity and rate of growth of neomucosa produced by intestinal patching can be significantly increased. There are three specific aims: (1) To determine if the growth of neomucosa is related to polyamine biosynthesis. Rabbits will undergo patching of the distal ileum and receive difluoromethylornithine (DFMO) to inhibit polyamine synthesis. If DFMO inhibits neomucosal growth, then known stimulators of polyamine biosynthesis might increase neomucosal growth. (2) To increase the rate of growth of neomucosa. Fifty percent intestinal resection with intestinal patching will be performed and urogastrone administered to stimulate neomucosal growth. These studies should determine if the rate of growth of neomucosa can be increased with these stimuli and whether or not this is related to an increase in polyamine synthesis. (3) To inhibit the marked contraction of the patched intestinal defect. Rabbits will undergo construction of a 25cm Thiry-Vella fistula with patching of the isolated loop. The loop will be perfused with either saline or Thiphenamil, a smooth muscle antagonist, and Cortisone acetate and Vitamin A will be administered parenterally to inhibit contraction of the defect. This study will determine if contraction of the intestinal defect can be prevented while epithelialization of the defect occurs. Neomucosal growth will be evaluated by gross and histologic measurements, mucosal DNA, RNA and diamine oxidase levels and functional studies. Tissue ornithine decarboxylase (ODC) and polyamine concentration will be measured to evaluate changes in polyamine synthesis. The goal of this project is to increase the rate of growth and yield of neomucosa from intestinal patching which would improve the clinical applicability of this technique.
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