Small intestinal transplantation represents a potentially therapeutic procedure for individuals with short gut syndrome. The purpose of this study was to develop a model for small intestinal transplantation in primates that is: technically feasible without microsurgery; consistent in the prevention of allograft rejection; functional in terms of nutrient absorption; and compatible with harvest for multiple organ procurement. First, autotransplantations on four rhesus monkeys were performed in order to study a variety of harvesting techniques and vascular anastomoses. Then, a study was performed with 14 heterotopic allotransplants in 4 baboons and 10 rhesus primates. The successful donor model consisted of division of the pancreas, harvesting the small bowel with a superior mesenteric artery and portal vein pedicle. The allograft vascular pedicle was anastomosed to the recipient's common iliac vessels in end-to-side fashion. The graft was transplanted as an out-of-continuity loop, both ends being exteriorized as stomas providing access for absorption studies and biopsy. Three immunosuppressive regimens were tested: (1) cyclosporine A (CyA) 20 mg/kg/d, solumedrol (SML) 2 mg/kg/d, and graft irradiation (150 rad) (n = 4); (2) CyA 20 mg/kg/d and SML 2 mg/kg/d (n = 3); and (3) CyA 40 mg/kg/d, SML 2 mg/kg/d, and azathioprine 5 mg/kg/d (n = 3). There were 4 deaths due to technical error in the first 24 hours. Weekly graft biopsy, serum CyA levels, complete blood count, and automated 24-channel serum analysis were performed. Grafts surviving greater than 14 days underwent absorption study via luminal perfusion with sucrose, maltose, dextrose, Pregestimil, xylose, and cyclosporine. Average graft survival was 7.5 (range, 6 to 9), 26.3 (range, 15 to 41), and 75.3 (range, 68 to 84) days, respectively, for the three immunosuppressive regiments. Absorption of carbohydrate was documented by serial measurement of serum glucose in fasted primates after infusion of maltose, dextrose, sucrose, and Pregestimil via the allograft. Absorption of xylose was similarly documented. Absorption of CyA was documented by serial serum CyA levels after luminal infusion of 40 mg/kg. A clinically applicable model for small intestinal harvest was developed that is consistent with multiple organ retrieval. A reliable allotransplantation technique and immunosuppressive regimen was developed resulting in long-term graft survival and functional absorption of carbohydrates and CyA.
- Intestinal transplantation
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health