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Progress in experimental porcine small-bowel transplantation
H Kaneko1, W Hancock, R T Schweizer
1Surgical Research Laboratory, Hartford Hospital, CT 06115.
Archives of Surgery (Chicago, Ill. : 1960)
|May 1, 1989
Summary
Successful small-bowel transplantation in large animals is achievable with optimized immunosuppression protocols. Intravenous cyclosporine followed by oral administration effectively prevented rejection and graft-versus-host disease, paving the way for clinical applications.
Area of Science:
- Surgical Transplantation
- Immunology
- Veterinary Medicine
Background:
- Small-bowel transplantation faces significant hurdles including technical challenges, allograft rejection, and graft-versus-host disease, limiting clinical use.
- Large animal models are crucial for addressing these complications and advancing transplantation techniques.
Purpose of the Study:
- To evaluate the efficacy of different immunosuppression strategies in a large animal model of small-bowel transplantation.
- To identify optimal protocols for preventing rejection and graft-versus-host disease in heterotopic and orthotopic small-bowel allografts.
Main Methods:
- Small bowel allografts were performed in 30 pigs, utilizing a combination of cyclosporine, prednisone, and azathioprine.
- Immunosuppression was administered via oral or intravenous routes, with specific attention to cyclosporine delivery timing and dosage.
- Graft survival, rejection episodes, graft-versus-host disease incidence, and sepsis-related mortality were monitored.
Main Results:
- Oral cyclosporine administration led to frequent rejection and graft-versus-host disease.
- A regimen of 30 days of intravenous cyclosporine followed by oral administration resulted in no rejection episodes and minimal graft-versus-host disease.
- Long-term survivors were achieved with this optimized immunosuppression protocol.
- Technical failures were infrequent, but sepsis (intra-abdominal abscess) caused mortality in 17% of subjects.
- Anastomosis of donor superior mesenteric vein to recipient portal vein showed no benefit over systemic venous drainage.
Conclusions:
- Adequate immunosuppression is critical for successful small-bowel transplantation in large animals.
- Intravenous administration of cyclosporine, followed by oral intake, represents a promising strategy to mitigate rejection and graft-versus-host disease.
- While sepsis remains a concern, these findings support the feasibility of small-bowel transplantation in large animal models, offering insights for human clinical application.