Recipient FK506 pretreatment regimens in rat small bowel transplantation: allograft survival, function, and systemic infection.
OBJECTIVE
Successful small bowel transplantation requires effective immunosuppression that preserves intestinal function but avoids opportunistic infection. This study aims to evaluate FK506 as a single immunosuppressant in different pretreatment regimens in a rat high responder strain combination.


METHODS
Lewis --> DA rat heterotopic small bowel transplantation was performed. Studied groups were (1) untreated control, n = 12; (2) FK-1, n = 8; (3) FK-3, n = 8. FK506 (2 mg/kg/d, intramuscularly) was given to the recipients for 1 day (FK-1) and 3 days (FK-3) before small bowel transplantation, followed by 2 weeks of subtherapeutic treatment (0.3 mg/kg/d, intramuscularly) after small bowel transplantation. Syngeneic small bowel transplantation also was performed (n = 8). FK blood levels, maltose absorption test, histology, and bacteriology were performed at different postoperative days.


RESULTS
Allograft survival was prolonged significantly with FK pretreatment, being more so in FK-3 group (FK-1, 22.2 +/- 1.5 d; FK-3, 40.7 +/- 14.1 d; control, 6.6 +/- 0.8 d; P< .01). In the first postoperative week, FK blood level was significantly higher in FK-3 group (19.8 +/- 1.5 ng/mL) than in FK-1 group (5.0 +/- 0.4 ng/mL; P < .05). There was no evidence of systemic infection in either FK-treated group. For maltose absorption, control allograft was abnormal on day 7 correlating to severely damaged intestinal architecture. In contrast, FK-treated allografts showed well-protected intestinal structure and normal absorption on days 7 and 21.


CONCLUSIONS
High FK506 blood levels in the first postoperative week, achieved with FK pretreatment, prolonged intestinal allograft survival and preserved intestinal structure and function without allowing systemic infection.
Guo
W H
WH
Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong SAR, PR China.
Tian
L
L
Yuen
Z W
ZW
Chan
K L
KL
Wo
J Y
JY
Nicholls
G
G
Dallman
M
M
Tam
P K
PK
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D007410:Intestinal Diseases / Q000601:surgery; D007421:Intestine, Small / Q000473:pathology / Q000601:surgery*; D008297:Male; D011183:Postoperative Complications / Q000382:microbiology* / Q000517:prevention & control; D011184:Postoperative Period; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000494:pharmacology*; D016378:Tissue Transplantation / Q000009:adverse effects / Q000379:methods*; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D016559:Tacrolimus