Morphology and function of canine small intestinal autografts: with particular interest in the influence of ex vivo graft irradiation.
The intestinal transplantation procedure obligates an early functional deficit in intestinal grafts. Graft irradiation has been used to modulate post-transplant immune reactions; however, irradiation may cause further deterioration of the function of the transplanted intestine. Using the canine model, we investigated the influence of the transplant procedures, with and without ex vivo graft irradiation, on early intestinal graft function and histopathology. Outbred hound dogs underwent autointestinal transplantation with (n=8) or without (n=5) 7.5 Gy ex vivo graft irradiation. Mucosal cytochrome P450 and P-glycoprotein, routine immunohistopathology, and intestinal absorptive function were studied. Weight gain was slow after surgery, but was comparable in the irradiated and nonirradiated groups. During the early post-transplant period, both groups showed defects in intestinal absorption, associated with decreased cytochrome P450 3A4 activity and reduced P-glycoprotein expression, regardless of graft irradiation. These changes returned to normal in both groups by day 28. Histopathologically, epithelial apoptosis showed a slight increase 1 hour after transplantation; however, there was no evidence of histopathologic abnormalities including arterial changes associated with irradiation. In addition, the frequency of T and B lymphocytes in the lamina propria were not significantly influenced by the transplant surgery or ex vivo irradiation. Thus, early after transplantation, intestinal function was impaired and effectiveness of orally administered immunosuppressive drugs was significantly altered. Graft irradiation did not induce further defects in intestinal function or cause histopathologic abnormalities.
Ishikawa
Takashi
T
Thomas, E., Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Iwanami
Kotaro
K
Okuda
Toyokazu
T
Zhu
Yue
Y
Fukuda
Akinari
A
Zhang
Shimin
S
Ou
Junhai
J
Nalesnik
Michael A
MA
Venkataramanan
Raman
R
Murase
Noriko
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016572:Cyclosporine / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D005260:Female; D006082:Graft Enhancement, Immunologic / Q000379:methods; D006084:Graft Rejection / Q000517:prevention & control*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000502:physiology / Q000528:radiation effects* / Q000637:transplantation*; D011829:Radiation Dosage; D014182:Transplantation, Autologous
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System