Mucosal glutamine utilization after small-bowel transplantation: an electrophysiologic study

Area of Science:

• Transplantation immunology
• Gastroenterology
• Surgical research

Background:

• Small bowel transplantation is crucial for recipient survival, but graft rejection remains a challenge.
• FK 506 (tacrolimus) is a key immunosuppressant in transplantation.
• Assessing graft functional competence post-transplantation is vital.

Purpose of the Study:

• To evaluate the efficacy of FK 506 in preventing small bowel allograft rejection.
• To assess the functional integrity of intestinal grafts using electrophysiologic measurements.
• To determine the impact of FK 506 dosage on long-term graft function and survival.

Main Methods:

• Orthotopic small bowel transplantation in Lewis rats using Brown-Norway allografts or syngeneic grafts.
• Administration of FK 506 in short-term or continuous regimens.
• Ex vivo electrophysiologic studies using Ussing chambers to measure mucosal ion transport (PD) and glutamine utilization.
• Measurement of mucosal resistance as an index of membrane integrity.

Main Results:

• Short-term FK 506 averted rejection and maintained graft function at 9 days post-transplant.
• Allografts undergoing rejection showed significantly decreased mucosal PD and blunted glutamine response.
• Continuous FK 506 treatment preserved normal mucosal PD and glutamine response at 60 days, similar to syngeneic grafts.
• Mucosal resistance was not significantly affected by rejection or short-term FK 506 therapy.

Conclusions:

• Allograft rejection severely impairs small bowel mucosal ion transport and glutamine utilization.
• FK 506 effectively controls rejection and preserves the electrophysiologic function of intestinal allografts.
• Continuous immunosuppression with FK 506 is essential for maintaining long-term graft functional competence and survival.