Small Intestinal Function Following Syngeneic Transplantation in the Rat

Improvements in immunosuppression have led to the use of small intestinal transplantation clinically. Previous studies have suggested that the transplantation process and immunosuppression with cyclosporin independently affect small intestinal function. This study describes the effects 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 cyclosporine (10 mg/kg) or vehicle on alternate days. Sham operated controls received treatment with vehicle. Animals were followed for 60 days monitoring weight gain, feed intake, intestinal permeability, in vivo absorption of dietary fat and carbohydrate, and at sacrifice in vitro transmural flux of 3-O-methyl-D-glucose. Weight gain, feed intake, and absorption of fat and carbohydrate from the diet were not altered by intestinal transplantation alone; transplantation plus cyclosporine treatment caused a slight reduction in dietary fat absorption. Both the transplant and transplant plus cyclosporine groups demonstrated increased permeability to 51Cr-EDTA and mannitol but not lactulose. Jejunal and ileal 3-O-methyl-D-glucose net transmural flux was decreased in both transplant and transplant plus cyclosporin groups. Intestinal transplantation and cyclosporin treatment reduce mucosal glucose transport and increase intestinal permeability. These altered transport characteristics could affect dietary choices and the selection of immunosuppressive drugs during clinical transplantation efforts, however, the overall impact on animal well-being was minimal, and support the continued study of intestinal transplantation for clinical application.