F. Abbiati

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large‐animal study

Abstract In this study we assessed functional changes (motility and absorption) of intestinal allografts in a large‐animal model of orthotopic small bowel transplantation in swine. Studies were performed on non‐rejecting animals in the early and late stages after transplantation and after induction of different grades of acute rejection. Immunosuppression consisted of oral FK506 and mycophenolate mofetil. In each study group we regulated drug administration, in terms of dosage and timing, in order to induce different grades of acute rejection or to prevent it. Migrating myoelectrical complexes were recorded in fasting animals so that motility could be assessed. Mucosal biopsy of the allograft and D‐xylose absorption tests were performed on the same day as the motility study. In the early stages following intestinal transplantation, we observed in non‐rejecting animals a slightly increased graft motility and a marked carbohydrate malabsorption. Recovery of the carbohydrate absorption capacity occurs within 2 months, but the persistence of diarrhea leads to partial malabsorption and to a lack of normal weight gain. Motility reduction correlates with the grade of acute rejection and becomes significant at a later stage, when rejection is severe. Allograft carbohydrate absorption, on the contrary, is markedly reduced in all rejecting pigs, irrespective of the grade of rejection. In summary, the early functional impairment of non‐rejecting animals has multifactorial causes due to surgery and immunosuppression (drug toxicity), and its occurrence suggests the need for specific guidelines for clinical early postoperative enteral feeding. The functional studies adopted here are helpful in defining the grade of functional impairment with or without acute rejection; however, they are not useful for early detection of ongoing acute rejection of the small bowel graft.

Tacrolimus and mycophenolate mofetil in pig small bowel transplantation: different protocols and their outcome

Abstract Clinical trials using FK 506 (Tacrolimus)-based immunosuppression after intestinal transplantation are underway. Long-term survivals have been limited by toxicity and infection due to the high dosage of FK 506 needed to control acute cellular rejection (ACR). The aim of this study is to assess, in a pig model of small bowel transplantation (SBTx), the efficacy and safety of two immunosuppressive protocols based on mycophenolate mofetil (MMF, CellCept) and different dosages of FK 506.

Development of a model of combined bone marrow and small bowel transplantation in swine

COMBINED donor bone marrow and solid-organ transplantation has been proposed to augment chimerism and to facilitate the development of donor-specific tolerance. Vertebral bodies (VBs) have been used as a favorable alternative to iliac crest as a source of bone marrow cells (BMCs). Herein we describe a method of swine bone marrow cell isolation from the VBs, liquid storage at 4°C, and transplantation 3 days after small bowel transplantation.