Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation

Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum bioma...

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Detalhes bibliográficos
Autores: Herrador, Lorena, González-Costello, José, Niubo Bosch, Jordi, Calatayud Samper, Laura, Maestro Benedicto, Alba, Farrero Torres, Marta, Blasco Peiró, Teresa, Almenar Bonet, Luis, Blázquez Bermejo, Zorba, Garrido Bravo, Iris, Gran Ipiña, Ferran, Grande Trillo, Antonio, Manito, Nicolas, Moreno González, Gabriel
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2025
País:España
Recursos:Universidad de Oviedo (UNIOVI)
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/224333
Acesso em linha:https://hdl.handle.net/2445/224333
Access Level:Acceso aberto
Palavra-chave:Inflamació
Apoptosi
Trasplantament cardíac
Inflammation
Apoptosis
Heart transplantation
Descrição
Resumo:Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor-recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced >= 2R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8-1003.3] vs. 65.3 [40.2-163.3] pg/mL; p = 0.04). A trend toward lower mtDNA/gDNA ratio was also observed in the same group (10.5 [5.4-24.6] vs. 6.5 [3.3-10.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury.

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