SMALL-INTESTINAL FUNCTION FOLLOWING SYNGENEIC TRANSPLANTATION IN THE RAT

Improvements in immunosuppression have led to the use of small intesti nal transplantation clinically. Previous studies have suggested that t he transplantation process and immunosuppression with cyclosporin inde pendently affect small intestinal function. This study describes the e ffects of syngeneic small intestinal transplantation and cyclosporine in rats on intestinal permeability and nutrient transport. Orthotopic transplantation of the small intestine was performed between syngeneic (Lewis) rats. Transplanted animals received chronic treatment with cy closporine (10 mg/kg) or vehicle on alternate days. Sham operated cont rols received treatment with vehicle. Animals were followed for 60 day s monitoring weight gain, feed intake, intestinal permeability, in viv o absorption of dietary fat and carbohydrate, and at sacrifice in vitr o transmural flux of 3-O-methyl-D-glucose. Weight gain, feed intake, a nd absorption of fat and carbohydrate from the diet were not altered b y intestinal transplantation alone; transplantation plus cyclosporine treatment caused a slight reduction in dietary fat absorption. Both th e transplant and transplant plus cyclosporine groups demonstrated incr eased permeability to Cr-51-EDTA and mannitol but not lactulose. Jejun al and ileal 3-O-methyl-D-glucose net transmural flux was decreased in both transplant and transplant plus cyclosporin groups. Intestinal tr ansplantation and cyclosporine treatment reduce mucosal glucose transp ort and increase intestinal permeability. These altered transport char acteristics could affect dietary choices and the selection of immunosu ppressive drugs during clinical transplantation efforts, however, the overall impact on animal well-being was minimal, and support the conti nued study of intestinal transplantation for clinical application. (C) 1996 Academic Press, Inc.