Background
Assessment of myocardial viability during ex situ heart perfusion (ESHP) is based
on the measurement of lactate concentrations. As this provides with limited information,
we sought to investigate the metabolic signature associated with donation after circulatory
death (DCD) and the impact of ESHP on the myocardial metabolome.
Methods
Porcine hearts were retrieved either after warm ischemia (DCD group, N = 6); after
brain-stem death (BSD group, N = 6); or without DCD nor BSD (Control group, N = 6).
Hearts were perfused using normothermic oxygenated blood for 240 minutes. Plasma and
myocardial samples were collected respectively every 30 and 60 minutes, and analyzed
by an untargeted metabolomic approach using liquid chromatography coupled to high-resolution
mass spectrometry.
Results
Median duration of warm ischemia was 23 minutes [19-29] in DCD animals. Lactate level
within myocardial biopsies was not significantly different between groups at T0 (p = 0.281), and remained stable over the 4-hour period of ESHP. More than 300 metabolites
were detected in plasma and heart biopsy samples. Compared to BSD animals, metabolomics
changes involving energy and nucleotide metabolisms were observed in plasma samples
of DCD animals before initiation of ESHP, whereas 2 metabolites (inosine monophosphate
and methylbutyrate) exhibited concentration changes in biopsy samples. Normalization
of DCD metabolic profile was remarkable after 4 hours of ESHP.
Conclusion
A specific metabolic profile was observed in DCD hearts, mainly characterized by an
increased nucleotide catabolism. DCD and BSD metabolomes proved normalized during
ESHP. Complementary investigations are needed to correlate these findings to cardiac
performances.
Keywords
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Article info
Publication history
Published online: February 22, 2023
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© 2023 International Society for Heart and Lung Transplantation. All rights reserved.
