Structure and function of small bowel allografts in the dog: immunosuppression with cyclosporin A.
Pairs of mongrel dogs received orthotopic total small bowel allografts. Half were treated with the immunosuppressive agent cyclosporin A and the other half were not. Ten untreated dogs survived a mean of 12.5 days (range from 7 to 25 days). They lost up to 30% of their initial body weight and rejection with hemorrhagic necrosis was usually the cause of graft failure. The mean survival of 11 dogs treated with cyclosporin A was 90.6 days (range 9 to 286 days) with early deaths being due to pneumonia or volvulus. Intestinal mucosa appeared normal, but there was some smooth muscle hypertrophy. Reconnection of lymph vessels was complete in all dogs examined more than 21 days after allografting. Two dogs survived for 203 and 221 days, respectively, and one dog remains alive and well 287 days after operation. The long-term survivors remained healthy, with steady body weights, formed stools, normal plasma protein values and xylose absorption curves that did not differ from those of autografted dogs. Roentgenography after a barium meal and follow-through study showed normal mucosa. The transit time was around 60 minutes (normal 150 minutes). Late, acute episodes of rejection occurred in two dogs, when blood levels of cyclosporin A were low (less than 400 ng/ml). Bowel mucosa showed ulceration and villous atrophy, with lymphoid infiltration, leading to malabsorption as a terminal event. Cyclosporin A is effective in increasing the duration of survival in dogs with small bowel allografts while maintaining essentially normal bowel structure and good function.