Protective effects of ex vivo graft radiation and tacrolimus on syngeneic transplanted rat small bowel motility.
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.
Schwarz
Nicolas T
NT
Department of Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Nakao
Atsunori
A
Nalesnik
Michael A
MA
Kalff
Jörg C
JC
Murase
Noriko
N
Bauer
Anthony J
AJ
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*
D007166:Immunosuppressive Agents; D016559:Tacrolimus