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Updated: Nov 27, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Apoptotic Markers in Donor Hearts After Brain Death vs Circulatory Death
Silvana F Marasco1, Jane F Arthur2, Ruchong Ou3
1Cardiothoracic Surgery Unit, The Alfred Hospital, Melbourne, Australia; Department of Surgery, Monash University, Melbourne, Australia.
Insights
Donation after circulatory death (DCD) hearts show reduced proapoptotic and inflammatory markers compared to brain dead donor (BDD) hearts, suggesting better preservation and reduced injury risk in cardiac transplantation.
Area of Science:
- Cardiology
- Transplantation Immunology
- Molecular Biology
Background:
- Donation after circulatory death (DCD) heart use is increasing in transplantation.
- Standardized myocardial preservation protocols for DCD hearts are lacking.
- Previous research indicated lower proapoptotic and proinflammatory markers in DCD atrial tissue compared to brain dead donor (BDD) hearts.
Purpose of the Study:
- To investigate proapoptotic and proinflammatory markers in DCD hearts.
- To correlate these markers with cardiac function post-preservation.
- To compare DCD hearts with BDD hearts regarding these molecular markers.
Main Methods:
- Prospective study of 11 human donor hearts (5 DCD, 6 BDD).
- Hearts preserved via continuous microperfusion for 4 hours.
- Messenger RNA (mRNA) analysis of cardiac tissues for apoptotic and inflammatory markers.
Main Results:
- BDD hearts showed significantly higher caspase-1, BNIP3, and NADPH oxidase mRNA expression than DCD hearts.
- These differences were more pronounced in older donors.
- Lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with improved right ventricular function post-reperfusion.
Conclusions:
- DCD hearts exhibit reduced activation of proapoptotic pathways and reactive oxygen species compared to BDD hearts.
- This suggests DCD hearts may be less susceptible to ischemic reperfusion injury.
- Findings support the potential viability and improved outcomes of DCD hearts in transplantation.
Background:
Use of donation after circulatory death (DCD) hearts is becoming more prevalent in cardiac transplantation. However, there is no standardized approach to myocardial preservation, and little data exists on ultrastructural changes in DCD hearts. We have previously identified increased proapoptotic and proinflammatory activity in brain dead donor (BDD) hearts that subsequently exhibit primary graft failure and lower levels in DCD left atrial tissue. This study further investigates these markers and correlates them with cardiac function in DCD hearts.
Methods:
This prospective study used donor hearts deemed unsuitable for transplant after gaining institutional ethics approval; 11 human hearts were obtained from 5 DCD donors and 6 BDDs. All hearts were preserved by continuous microperfusion for 4 hours with a cold crystalloid solution and then were evaluated on a blood perfusion bench rig. After 4 hours perfusion and working assessment, tissues from all cardiac chambers were stored for later messenger RNA (mRNA) analysis for proapoptotic and proinflammatory markers.
Results:
Significantly raised levels of caspase-1, BNIP3, and NADPH oxidase mRNA expression were identified in cardiac chambers from BDD hearts compared to DCD hearts, and these differences were exaggerated in older donors. In the pooled analysis, lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with developed pressure at 1 hour after reperfusion in the right ventricle, but not the left.
Conclusion:
Compared to BDD hearts, DCD hearts exhibit less stimulation of proapoptotic cascades and reactive oxygen species, potentially reducing their susceptibility to ischemic reperfusion injury.
