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Updated: Apr 18, 2026
Author Spotlight: Enhancing Donor Heart Preservation Through Isolated Rat Heart Perfusion Studies
Published on: October 4, 2024
Transplantation of donor hearts after circulatory or brain death in a rat model
Shiliang Li1, Sivakkanan Loganathan2, Sevil Korkmaz1
1Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Insights
Brain-dead hearts exhibit significant inflammation and damage compared to hearts from donors after circulatory determination of death (DCDD). This suggests DCDD hearts may be more suitable for transplantation despite similar initial function.
Area of Science:
- Cardiovascular Surgery
- Transplantation Immunology
- Organ Preservation
Background:
- Heart transplantation is the sole curative option for end-stage heart failure.
- The limited donor pool necessitates exploring alternative organ sources.
- Donors after circulatory determination of death (DCDD) present a potential solution to donor scarcity.
Purpose of the Study:
- To investigate the molecular mechanisms and pathological changes in hearts from brain-dead donors versus DCDD donors.
- To assess the viability and suitability of DCDD hearts for transplantation.
- To compare inflammatory and apoptotic markers in hearts subjected to different donor conditions.
Main Methods:
- Rat models were used to simulate brain death and DCDD conditions.
- Hearts were preserved using Custodiol solution and stored at 4°C.
- Heterotopic heart transplantation was performed to evaluate cardiac function.
- Molecular analysis included assessment of inflammatory and apoptotic markers (mRNA and protein levels).
Main Results:
- Brain death significantly impaired left-ventricular contractility and relaxation compared to controls.
- Both brain-dead and DCDD hearts showed decreased systolic function and prolonged relaxation post-transplantation.
- Brain-dead hearts exhibited significantly higher levels of inflammatory markers (TNF-α, COX-2, NF-κB, iNOS) and apoptosis markers (caspase-3).
- Histological analysis revealed increased inflammatory cell infiltration, edema, necrosis, and DNA damage in brain-dead hearts.
Conclusions:
- While functional outcomes were similar initially, brain-dead hearts showed substantial myocardial damage.
- Brain death induced significant inflammatory responses and apoptotic pathways not observed to the same extent in DCDD hearts.
- These findings highlight critical differences in myocardial injury between brain-dead and DCDD donors, impacting organ suitability for transplantation.
Background:
Heart transplantation represents the only curative treatment for end-stage heart failure. Presently, the donor pool is restricted to brain-dead donors. Based on the lack of suitable donors and the increasing number of patients, we investigated some molecular pathomechanisms of the potential use of hearts after circulatory determination of death (DCDD) in transplantation.
Materials And Methods:
Rats were either maintained brain death for 5 h by inflation of a subdurally placed balloon catheter (n = 6) or subjected to cardiac arrest by exsanguinations (n = 6). Additionally, a control group was used (n = 9). Then the hearts were perfused with a cold preservation solution (Custodiol), explanted, stored at 4°C in Custodiol, and heterotopically transplanted.
Results:
Brain death was associated with decreased left-ventricular contractility (dP/dtmax: 4895 ± 505 versus 8037 ± 565 mm Hg/s; ejection fraction: 27 ± 5 versus 44 ± 5%; Emax: 2.2 ± 0.3 versus 4.2 ± 0.3 mm Hg/μL; preload recruitable stroke work: 59 ± 5 versus 96 ± 6 mm Hg; 5 h after brain death versus before brain death; P < 0.05) and impaired cardiac relaxation (dP/dtmin: -4734 ± 575 versus -9404 ± 550 mm Hg/s and prolonged Tau, P < 0.05) compared with controls. After transplantation, significantly decreased systolic function and prolonged Tau were observed in brain-dead and DCDD groups compared with those in controls. Tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor-κB, inducible-NOS, and caspase-3 messenger RNA and protein-levels were significantly increased in the brain-dead compared with both control and DCDD groups. Additionally, marked myocardial inflammatory cell infiltration, edema, necrosis, and DNA-strand breaks were observed in the brain-dead group.
Conclusions:
Our results show that despite the similar functional outcome in DCDD and brain-dead groups, brain-dead hearts showed marked myocardial inflammatory cell infiltration, edema, necrosis, DNA-strand breaks, and increased transcriptional and posttranscriptional expression for markers of apoptosis and inflammatory signaling pathways.
