title: Protective effects of ex vivo graft radiation and tacrolimus on syngeneic transplanted rat small bowel motility.
abstract: BACKGROUND
  Intestinal transplantation is unduly complicated by the nontolerogenic properties of the gut-associated lymphoid tissue. Because simultaneous graft irradiation and bone marrow infusion significantly prolong the survival of the small bowel transplanted animal, our objective was to determine the functional motility effects of the immune modulating, graft irradiation procedure in the presence and absence of tacrolimus immunosuppression.
  
  
  METHODS
  Four groups of syngeneic orthotopic small bowel transplanted animals were studied 48 hours after operations (untreated, tacrolimus, ex vivo graft irradiation, and tacrolimus + irradiation) and compared with controls. Histologic analysis was performed for mucosal apoptosis and neutrophilic infiltration into the muscularis externa. Gastrointestinal in vivo transit and in vitro circular muscle strip contractions were quantified in response to bethanechol (0.3-300 micromol/L).
  
  
  RESULTS
  Graft irradiation ex vivo alone or in the presence of tacrolimus significantly increases (> 10-fold) the number of apoptotic mucosal cells after transplantation. Functional measurements showed that transplantation resulted in a significant delay in gastrointestinal transit and a decrease in muscle strip contractility. Tacrolimus and graft irradiation significantly ameliorated the transplant-induced dysfunction.
  
  
  CONCLUSIONS
  Given the endowed propensity of mucosal regeneration, the immunologic and functional benefits of ex vivo graft irradiation appear to outweigh the detrimental effects to the mucosa.
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Nicolas T
authors.initials: NT
authors.lastname: Schwarz
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalesnik
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
mesh_terms: D000818:Animals; D005769:Gastrointestinal Motility; D005772:Gastrointestinal Transit; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000503:physiopathology / Q000528:radiation effects* / Q000637:transplantation*; D008297:Male; D020556:Neutrophil Infiltration; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus