EVALUATION OF NEOMUCOSA AND FACTORS AFFECTING ITS GROWTH

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.