DCD in intestinal transplantation: the path to prove its validity in both experimental and clinical models

Introduction: DCD has not been considered as a valid alternative for intestinal transplantation (IT). However, the use of normothermia has recently improved the results of the classic cold perfusion in other organs under this condition. Our aim was double: to test the viability and function of the intestinal grafts using normothermic regional perfusion (NRP) in an experimental model and to assess ischemic-reperfusion injury (IRI) of the small bowel in human DCD. Methods: We used an experimental porcine model with 8 donor-recipient pairs (25.5 ± 2.5 kg). Donors were supported using a NRP for abdominal organs after the withdrawal of their life sustaining treatment. The small intestine was heterotopically transplanted into the recipients and they were followed-up for two weeks, using tacrolimus for daily immunosuppression. Blood and intestinal samples were obtained repeatedly throughout the procedure and 1, 2, 7 and 14 days after. IRI was evaluated using the Park-Chiu score (PCS) in samples taken during NRP and up to 48 hours after IT. Samples from 7 and 14 days were analyzed to assess graft rejection and GVHD. The absorptive function of the grafts was tested at the endpoint. Glycemia from the draining veins of the graft was compared with that from the native small bowel and peripheral blood 15, 30 and 60 minutes after intra-graft glucose administration. The small intestines from 26 human DCDs were also sampled for histological analysis while other organs were procured for transplantation with NRP after 30 and 60 minutes. Results: All the intestines were successfully procured and presented an excellent appearance. One case was excluded due to venous stenosis. 6 animals (86%) reached the endpoint in good conditions. Grafts conserved architecture during NRP, with edema at the villus tip (PCS-1) only in two samples after 1h. The highest PCS was observed 1h after reperfusion, with denuded villi (PCS-4) in 3 samples (43%). All grafts recovered, with no or very subtle alterations after 48 hours. Five recipients (71%) did not show rejection signs at any time. 2 cases (29%) expressed mild rejection after 7 days. At the endpoint, one of them had recovered but the other had progressed to severe acute cellular rejection (14%). Grafts’ glycemia reached its maximum 30 minutes after glucose administration, demostrating their absorption capacity. All intestines from human donors appeared macroscopically normal. Their samples did not show any significant IRI in 80% of the cases. PCS score was 1.23 [0-3] after 30 minutes and 1.65 [0-4] after 60 minutes. Conclusion: This experimental model postulate DCD donation under NRP as an alternative source of organs to address the mismatch between the waiting list for IT and the scarcity of donors. Its clinical and functional results appear to be comparable to those of other organ procurement techniques. The analysis of the human samples suggests that this approach could be successfully translated to the clinical setting.