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Updated: Oct 4, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Critical warm ischemia time point for cardiac donation after circulatory death
Silvia Sánchez-Cámara1,2, Mari C Asensio-López1,3, Mario Royo-Villanova1,2,4
1Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Insights
Donation after circulatory death (DCD) heart transplantation is viable, as critical warm ischemia time up to 10 minutes post-circulatory arrest shows no significant cellular compromise. This supports DCD donor utilization for heart transplants.
Area of Science:
- Cardiology
- Transplantation Medicine
- Biochemistry
Background:
- Donation after circulatory death (DCD) offers a solution to donor shortages in heart transplantation.
- The critical warm ischemia time (WIT) in DCD donors remains a concern for myocardial viability.
Purpose of the Study:
- To determine the critical warm ischemia time in DCD donors by assessing in vivo biochemical changes.
- To evaluate the impact of WIT on cardiomyocyte function and viability.
Main Methods:
- Serial endomyocardial biopsies in 16 DCD non-cardiac donors before and after circulatory arrest (CA).
- Assessment of calcium homeostasis, mitochondrial function, and cellular viability.
- Analysis of biochemical markers including cAMP-dependent protein kinase-A, SERCA2, and caspase activity.
Main Results:
- No significant deterioration in cardiac parameters was observed at the time of CA (median 9 min).
- Within 10 minutes after CA, significant decreases in protein kinase-A phosphorylation, SERCA2, and mitochondrial complex II/IV activities were noted, alongside increased caspase 3/7 activity.
- Cardiomyocyte function and viability remained largely unaffected during the initial 10 minutes post-CA.
Conclusions:
- The initial 10 minutes following circulatory arrest in DCD donors do not significantly compromise cardiomyocyte function or viability.
- These findings support the safe incorporation of DCD donors into heart transplant programs, potentially expanding donor availability.
Abstract:
Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.
