Long-Term Survival of Orthotopic Small-Bowel Allografts Using Cyclosporin A

Abstract

Although small-bowel transplantation was first described by Lillihei nearly 30 years ago (Lillihei et al. 1959), clinical small-bowel transplantation has to date been limited to fewer than ten reported cases. The major obstacle to successful human small-bowel transplantation has been the lack of an effective immunosuppressive regimen for control of graft rejection. Early experimental and clinical attempts at intestinal transplantation using corticosteroids, azathioprine, and antilymphocyte serum failed to achieve long-term graft and recipient survival (Preston et al. 1966; Alican et al. 1971; Hardy et al. 1970). The recent successful use of cyclosporine A (CsA) in transplantation of other vascularized organ grafts has led to its use in small- bowel transplantation as well. With CsA, long-term survival of accessory, defunctionalized intestinal allografts has been achieved (Kirkman et al. 1984). However, long-term healthy survival of graft recipients who are entirely dependent upon the transplanted small intestine for nutritional intake has yet to be demonstrated consistently. A rat model of small-bowel transplantation was therefore used to determine if rejection can be satisfactorily controlled using CsA so as to permit normal recipient growth and maintenance of a normal nutritional state.

Supported by The National Institutes of Arthritis, Metabolism, and Digestive Diseases (Grant No. AM27332).