title: 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.
authors.affiliation: Department of Surgery, University of Pavia and IRCCS Policlinico San Matteo, P. le Golgi 2, 27100 Pavia, Italy. m.alessiani@unipv.it
authors.forename: Mario
authors.initials: M
authors.lastname: Alessiani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Ponti
authors.forename: Filiberto
authors.initials: F
authors.lastname: Fayer
authors.forename: Francesca
authors.initials: F
authors.lastname: Abbiati
authors.forename: Sandro
authors.initials: S
authors.lastname: Zonta
authors.forename: Ermanno
authors.initials: E
authors.lastname: Zitelli
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morbini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Poggi
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Ilaria
authors.initials: I
authors.lastname: Blangetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Dionigi
authors.forename: Aris
authors.initials: A
authors.lastname: Zonta
mesh_terms: D000208:Acute Disease; D000818:Animals; D005769:Gastrointestinal Motility; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000503:physiopathology / Q000601:surgery / Q000637:transplantation*; D023421:Models, Animal; D013552:Swine; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents