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Cardiac transplantation: better graft eligibility criteria thanks to metabolomics?


​In a study conducted by a team from the Marie Lannelongue Hospital, researchers from the SPI (DMTS) have established a difference between the metabolomic profiles of heart grafts harvested from pigs in a state of brain death or dead after controlled circulatory arrest. Given the downward trend in the number of donors who have died in a state of brain death, this work is helping to explore and validate the use of hearts harvested from people who have died after controlled circulatory arrest as a new source of transplants.

Published on 15 November 2023

​Countries such as the United Kingdom and Australia authorise the removal of a heart graft from a person who has died after a controlled circulatory arrest (donation after circulatory-determined death, DCD). In France, only transplants taken from people in a state of encephalic death (brain-stem death, BSD) are authorised, as the risk of heart failure occurring after DCD transplant is high (39% in the 48 hours following the transplant). However, the downward trend in the number of people dying in a state of BSD means that we need to think about developing other types of transplant. 

How can we anticipate possible failures in DCD heart transplantation?

Most transplant teams performing this type of transplant assess the viability of the myocardium during the ex situ cardiac perfusion phase, which is necessary to preserve the heart for transplantation. The method, based on the measurement of lactate concentrations, has its limitations; it gives only a glimpse of the metabolic state of hearts. 

A team from the Marie Lannelongue Hospital (Université Paris-Saclay, Le Plessis-Robinson), in collaboration with a team from LI-MS (SPI/DMTS), led by Benoît Colsch and specialising in cutting-edge metabolomics methods, set out to find out if there were biomarkers that would give a better idea of the metabolic state of transplanted hearts. They carried out a study using a porcine model of heart transplantation.

The researchers demonstrated that the DCD hearts have a specific metabolic profile, mainly characterised by an increase in purine metabolism. The changes in metabolism observed were reversible during ex vivo perfusion and tended to 'normalise' after 3 hours, in other words to resemble the hearts of individuals in a state of brain death.  

Further studies are needed to establish a correlation between these observations and heart transplant performance. If this is established, then the biomarkers discovered could be essential for transplant teams to judge the eligibility of heart grafts.​

Frédéric-Joliot Institute researcher contact:

Benoît​​ Colsch (benoit.colsch@cea.fr)


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