Abstract

The purpose of this study was to determine whether small intestinal transplantation could be considered as an alternative in the treatment of patients suffering from the short-bowel syndrome. The site of absorption of oral cyclosporine A was determined as were the changes that follow small intestinal transplantation. The interactions between the lipophilic cyclosporine A molecule and fat emulsion solutions used for total parenteral nutrition were investigated. Finally, a technique for harvesting the entire small bowel in man was developed. The absorption of oral cyclosporine A in normal dogs, and in bowel-resected, autotransplanted, and allotransplanted dogs was determined. Cyclosporine A levels were monitored in all animals. This demonstrated that cyclosporine A is absorbed through the small bowel and carried through the lymphatics; that absorption is decreased to 40 percent of normal after autotransplantation or allotransplantation without rejection. Rejection further hampers cyclosporine A absorption. Administration of olive oil alone enhances absorption of cyclosporine A. We also administered cyclosporine A IV to five dogs, with and without a concomitant infusion of fat emulsion solution (Intralipid). No changes in plasma cyclosporine A levels, in the clearance of cyclosporine A, or in the in vivo distribution of cyclosporine A were noted. Finally, dissections in six cadavers and in four brain-dead organ donors were performed, and a reproducible technique for harvesting the small bowel in man was established. In selected patients with the short-bowel syndrome, small intestinal transplant may be considered as an alternative therapy to home total parenteral nutrition.

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