Small Intestinal Allografts Research Articles

Maltose absorption as an indicator of small-intestinal allograft rejection

Maltose and lactose absorption, which require an intact brush border for breakdown and absorption as glucose, was evaluated as a function test to monitor the integrity of the small-bowel graft. Using the rat model of accessory small-bowel transplantation, absorption tests (in the form of an oral glucose tolerance test) were performed on iso- and allografts with either portal (PP-A) or caval venous drainage (PC-A). In isografts the absorption of maltose was found to be reproducible and not influenced by the type of venous drainage. This was not the case with the use of lactose which thus was not studied further. Allografts with PC-A demonstrated a reduction in their capacity for maltose absorption on the fifth postoperative day, as the glucose peak at 30 min (T30) was significantly blunted in comparison to that for isografts with PC-A (167 mg% ± 12 vs 204 mg% ± 8). Functional impairment preceded histologic changes which did not arise before the sixth-to-seventh postoperative day in rats with PC-A. Allografts with PP-A absorbed maltose on the fifth postoperative day nearly as effectively as did isografts (T30 min: 185 mg% ± 14 vs 213 mg% ± 8). By the ninth postoperative day, the serum glucose curve after maltose administration was flattened for grafts with PC-A (T30 min: 137 mg% ± 11) which were rejected acutely (host's death) after 11.8 days ± 0.45. A similar impairment of maltose absorption was not seen in the PP-A group (chronic graft rejection after 22.8 days ± 1.8) until the 15th postoperative day. These results suggest that maltose absorption becomes impaired before the clinical appearance of rejection and its histologic alterations. The maltose absorption test effectively predicts rejection and monitors the function of the intestinal graft in this animal model.

Prolonged survival of canine orthotopic small intestinal allografts preserved for 24 hours by hypothermic bloodless perfusion.

Whole orthotopic small intestinal transplants were carried out into moderately immunosuppressed dogs. Survival time was compared between the dogs with fresh grafts and those with grafts preserved by hypothermic bloodless pulsatile perfusion for 24 hours. Two perfusates were used during preservation; (1) cryoprecipitated pooled dog plasma or (2) human plasmanate. Survival was significantly better in the dogs which received the preserved grafts. The best survival time was achieved in intestinal allografts perfused with human plasmanate (mean survival, 45 days, the longest being 67 days). These results suggest that significant prolongation of allograft survival in moderately immunosuppressed animals might be achieved by modification of the immunogenicity of grafts either by preservation or by binding with non-specific xenogeneic antibodies in a perfusate solution.

Problems in absorption and immunosuppression after entire intestinal allotransplantation

Orthotopic entire small intestine allografts were transplanted in twenty dogs. Ten of these animals received immunosuppressive drugs. Allograft function was compared with that of other dogs subjected to complete intestinal denervation and lymphatic interruption. Dogs with denervated intestine showed decreased d-xylose absorption with reversal to normal rates within four months. Groups receiving allografts also showed depressed function which persisted for up to five weeks. Interestingly, dogs with untreated allografts showed no significant pathologic changes even though survival ranged from one to four weeks. In contrast, some dogs who received immunosuppressive drugs showed manifestations of organ rejection. Although we could not clearly demonstrate a graft versus host reaction in untreated allografts, it appears that entire small intestinal allografts, in the absence of these immunosuppressive drugs, can precipitate such a reaction. This phenomenon is believed to be related to the abundant lymphatic tissue found in the intestine.