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Updated: Jun 17, 2026
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation
Lorena Herrador1,2, José González-Costello1,2,3, Jordi Niubo-Bosch2,4
1Heart Failure and Heart Transplant Unit, Cardiology Department, Bio-Heart Cardiovascular Diseases Research Group, Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Insights
Lower Caspase-3 levels in heart donor serum are linked to primary graft dysfunction in recipients. This suggests donor apoptosis may protect the transplanted heart from injury.
Area of Science:
- Transplantation immunology
- Cellular biology
- Biomarker discovery
Background:
- Primary graft dysfunction (PGD) is a leading cause of death after heart transplantation (HTx).
- Donor-related factors influencing PGD risk require further investigation for improved organ selection and outcomes.
Purpose of the Study:
- To investigate the association between donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients.
- To explore potential donor-derived mechanisms impacting graft survival post-transplantation.
Main Methods:
- Retrospective, multicenter observational study of 39 brain-dead donor-recipient pairs (2013-2019).
- Analysis of donor serum for inflammatory cytokines, cell death markers (Caspase-3), mitochondrial DNA (mtDNA), and genomic DNA (gDNA).
Main Results:
- Donors whose recipients developed severe PGD had significantly lower serum Caspase-3 levels (p=0.04).
- A trend towards a lower mtDNA/gDNA ratio was observed in donors of recipients with PGD (p=0.067).
- Lower Caspase-3 levels were significantly associated with severe PGD development.
Conclusions:
- Sublethal activation of apoptotic pathways in heart donors may play a protective role in graft tolerance to ischemic injury.
- Donor serum Caspase-3 levels could serve as a predictive biomarker for PGD risk in heart transplant recipients.
Abstract:
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.
