Recipient FK506 pretreatment regimens in rat small bowel transplantation: allograft survival, function, and systemic infection

J Pediatr Surg. 2000 Nov;35(11):1600-5. doi: 10.1053/jpsu.2000.18326.

Abstract

Purpose: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Graft Rejection
  • Graft Survival
  • Intestinal Diseases / surgery
  • Intestine, Small / pathology
  • Intestine, Small / surgery*
  • Male
  • Postoperative Complications / microbiology*
  • Postoperative Complications / prevention & control
  • Postoperative Period
  • Preoperative Care / methods
  • Probability
  • Rats
  • Rats, Inbred Lew
  • Sensitivity and Specificity
  • Tacrolimus / pharmacology*
  • Tissue Transplantation / adverse effects
  • Tissue Transplantation / methods*
  • Transplantation Immunology / physiology*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Tacrolimus