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Updated: Jul 2, 2026
Using a Chemical Biopsy for Graft Quality Assessment
Published on: June 17, 2020
Distinct metabolomic and lipidomic profiles across donation after circulatory death recovery strategies reveal a
Elizabeth J Bashian1, Sariah Hyacinth2, Charles D Nicoli3
1University of Colorado, Division of Cardiothoracic Surgery, Aurora, Colorado.
Insights
Donation after circulatory death (DCD) heart transplantation uses varied recovery methods. Post-transplant analysis reveals distinct metabolic profiles linked to procurement strategies and graft injury, offering insights into preservation.
Area of Science:
- Cardiology
- Transplantation Immunology
- Metabolomics
Background:
- Donation after circulatory death (DCD) heart transplantation expands donor availability.
- Understanding the biological impact of different DCD heart recovery strategies is crucial.
Purpose of the Study:
- To investigate the metabolomic and lipidomic consequences of various DCD heart procurement methods.
- To identify metabolic signatures associated with primary graft dysfunction (PGD) after DCD heart transplantation.
Main Methods:
- Metabolomic and lipidomic profiling of coronary sinus blood from DCD heart transplant recipients.
- Analysis of samples from recipients undergoing thoraco-abdominal normothermic regional perfusion, normothermic machine perfusion, or cold oxygenated rapid recovery.
- Statistical analysis including partial least squares discriminant analysis to identify distinct metabolic clusters.
Main Results:
- Distinct metabolomic profiles were observed based on procurement strategy.
- Primary graft dysfunction (PGD) was associated with depletion of TCA cycle and redox metabolites.
- PGD correlated with accumulation of acylcarnitines and amino-acid catabolic intermediates, indicating impaired mitochondrial energetics and oxidative stress.
Conclusions:
- Procurement strategies influence the metabolic phenotype of DCD hearts.
- A common metabolic signature of impaired mitochondrial energetics, oxidative stress, and phospholipid remodeling characterizes PGD.
- Metabolic profiling may offer targets for improving graft preservation and stratifying PGD risk.
Abstract:
Donation after circulatory death (DCD) heart transplantation has expanded the donor pool, but the biologic consequences of different recovery strategies remain incompletely understood. Using coronary sinus blood obtained immediately following reperfusion, we performed metabolomic profiling in 31 DCD heart transplant recipients and lipidomic profiling in a nested cohort of 11 recipients with various DCD procurement methods as follows: thoraco-abdominal normothermic regional perfusion (n=10); normothermic machine perfusion (n=10), or cold oxygenated rapid recovery (n=11). Partial least squares discriminant analysis demonstrated distinct metabolomic clustering according to procurement strategy. Moderate or severe PGD occurred in 16 recipients (51.6%) and was associated with depletion of tricarboxylic acid (TCA) cycle and redox metabolites together with accumulation of acylcarnitines and amino-acid catabolic intermediates, consistent with impaired mitochondrial energetics, oxidative stress, and membrane injury. Despite distinct procurement-specific metabolic phenotypes, PGD was associated with a common metabolic signature characterized by impaired mitochondrial energetics, oxidative stress, acylcarnitine accumulation, and phospholipid remodeling, highlighting potential mechanistic targets for graft preservation and risk stratification.
