Metabolic Choreography of Energy Substrates During DCD Heart Perfusion.

Autor:	Trimigno A; Olaris, Inc., Framingham, MA., Zhao J; Olaris, Inc., Framingham, MA., Michaud WA; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Paneitz DC; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Chukwudi C; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., D'Alessandro DA; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Lewis GD; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Minie NF; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Catricala JP; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Vincent DE; VentriFlo, Inc., Pelham, NH., Lopera Higuita M; Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Shriner Children's Boston, Boston, MA., Bolger-Chen M; Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Shriner Children's Boston, Boston, MA., Tessier SN; Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Shriner Children's Boston, Boston, MA., Li S; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., O'Day EM; Olaris, Inc., Framingham, MA., Osho AA; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA., Rabi SA; Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA.
Jazyk:	angličtina
Zdroj:	Transplantation direct [Transplant Direct] 2024 Aug 29; Vol. 10 (9), pp. e1704. Date of Electronic Publication: 2024 Aug 29 (Print Publication: 2024).
DOI:	10.1097/TXD.0000000000001704
Abstrakt:	Background: The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking. Methods: Metabolites were analyzed using 1-dimensional 1 H and 2-dimensional 13 C- 1 H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways. Results: Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate. Conclusions: Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion. Competing Interests: A.T., J.Z., and E.M.O. are employees of Olaris, Inc and have ownership and salary interest in the company. The other authors declare no conflicts of interest. (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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