Changes in fecal fat excretion from allo-intestine transplanted rats after discontinuance of immunosuppressive agents

Abstract:

We have previously shown in a rat model of segmental small bowel transplantation, that an ileal graft was more favorable for lipid absorption than a jejunal graft. In the present study, we investigated changes in the lipid absorption of allo-ileal grafts after the withdrawal of an immunosuppressant (methyldeoxyspergualin; given for 1 or 2 weeks at 2.5 mg/kg per day) and compared the findings with the results of histological examinations. Heterotopic segmental small bowel transplantation (SBT) was performed using cuff anastomoses in the inbred rat strain combination DA (RT1^a) and LEW (RT1^l). Orthotopic SBT was performed as reconstruction SBT. Reconstruction after resection of the original intestinal tract of the recipient was performed on the seventh day after heterotopic segmental ileal grafting. For the histological evaluation of graft rejection, we performed biopsies in the heterotopic model and autopsies in the orthotopic model. Fecal fat excretion from the orthotopically reconstructed recipients was measured by Folch's method. One- and 2-week use of methyldeoxyspergualin allowed the heterotopic allografts to remain intact histologically for 16.8 ± 5.6 and 25.3 ± 3.3 (mean ± SD) days, respectively, whereas the grafts were rejected at 7.3 ± 1.1 days when the immunosuppressive drug was not used. All the recipients in the orthotopic group had died by 19 days after reconstruction. After discontinuance of the immunosuppressive agent, fat excretion in feces in the surviving orthotopic grafted rats had increased markedly prior to histologically assessed heterotopic graft rejection. Evaluation of fecal lipid excretion may be a useful parameter for detecting graft rejection in rats.