Related Experiment Video
Updated: Aug 12, 2025
Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment
Published on: May 10, 2022
Experimental Assessment of Intestinal Damage in Controlled Donation After Circulatory Death for Visceral
Pablo Stringa1,2,3,4, Leandro Emmanuel Vecchio Dezillio3,4, Paloma Talayero5
1Transplant Group, La Paz University Hospital Health Research Institute (IdiPAZ), Madrid, Spain.
Abstract:
There is an urgent need to address the shortage of potential multivisceral grafts in order to reduce the average time in waiting list. Since donation after circulatory death (DCD) has been successfully employed for other solid organs, a thorough evaluation of the use of intestinal grafts from DCD is warranted. Here, we have generated a model of Maastricht III DCD in rodents, focusing on the viability of intestinal and multivisceral grafts at five (DCD5) and twenty (DCD20) minutes of cardiac arrest compared to living and brain death donors. DCD groups exhibited time-dependent damage. DCD20 generated substantial intestinal mucosal injury and decreased number of Goblet cells whereas grafts from DCD5 closely resemble those of brain death and living donors groups in terms intestinal morphology, expression of tight junction proteins and number of Paneth and Globet cells. Upon transplantation, intestines from DCD5 showed increased ischemia/reperfusion damage compared to living donor grafts, however mucosal integrity was recovered 48 h after transplantation. No differences in terms of graft rejection, gene expression and absorptive function between DCD5 and living donor were observed at 7 post-transplant days. Collectively, our results highlight DCD as a possible strategy to increase multivisceral donation and transplantation procedures.
Insights
Donation after circulatory death (DCD) intestinal grafts show promise for increasing organ availability. Early DCD grafts (5 minutes) demonstrate viability and recover function post-transplant, offering a potential solution to donor shortages.
Area of Science:
- Transplantation immunology
- Gastroenterology
- Organ donation research
Background:
- A critical shortage of multivisceral grafts exists, increasing patient waiting times.
- Donation after circulatory death (DCD) is established for other organs, suggesting potential for intestinal grafts.
- Evaluating DCD intestinal grafts is crucial to address donor organ scarcity.
Purpose of the Study:
- To assess the viability of intestinal grafts from donation after circulatory death (DCD) donors.
- To compare DCD grafts with different cardiac arrest times (5 and 20 minutes) against living and brain death donors.
- To evaluate the functional recovery and immunological acceptance of DCD intestinal grafts post-transplantation.
Main Methods:
- Generation of a rodent model of Maastricht III DCD.
- Assessment of intestinal and multivisceral graft viability at 5 (DCD5) and 20 (DCD20) minutes post-cardiac arrest.
- Histological analysis, assessment of tight junction proteins, and cell counts (Goblet, Paneth cells).
- Transplantation of DCD5 grafts and comparison with living donor grafts regarding ischemia/reperfusion injury, mucosal integrity, rejection, gene expression, and absorptive function.
Main Results:
- DCD grafts showed time-dependent damage, with DCD20 exhibiting significant mucosal injury and goblet cell loss.
- DCD5 grafts maintained intestinal morphology, tight junction protein expression, and cell counts comparable to controls.
- Post-transplant, DCD5 grafts experienced initial ischemia/reperfusion damage but recovered mucosal integrity within 48 hours.
- No significant differences in graft rejection, gene expression, or absorptive function were observed between DCD5 and living donor grafts at 7 days post-transplant.
Conclusions:
- Intestinal grafts from DCD donors, particularly with shorter cardiac arrest times (5 minutes), are viable.
- DCD5 grafts demonstrate functional recovery and immunological compatibility post-transplantation, similar to living donor grafts.
- DCD represents a viable strategy to expand the pool of multivisceral grafts for transplantation.
