Document Type

Article

Publication Date

2-22-2025

Publication Title

Analytica chimica acta

Keywords

JGM, Animals, Male, Swine, Solid Phase Microextraction, Metabolomics, Myocardium, Dialysis, Heart, Organ Preservation, Perfusion

JAX Source

Anal Chim Acta. 2025;1340:343581

Volume

1340

First Page

343581

Last Page

343581

ISSN

1873-4324

PMID

39863306

DOI

https://doi.org/10.1016/j.aca.2024.343581

Abstract

BACKGROUND: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.

RESULTS: Male Yorkshire porcine hearts were subjected to ESHP for 8 h with or without dialysis. Alterations in metabolism were studied with an innovative in vivo solid-phase microextraction (SPME) technology coupled with global metabolite profiling at 15 min, 1.5, 4, and 8 h of perfusion. Bio-SPME sampling was performed by inserting SPME fibres coated with a PAN-based extraction phase containing mixed-mode (C8+benzenesulfonic acid) functionalities into the myocardium to a depth of their entire 8 mm coating or immersing them in the perfusate, followed by a 20-min extraction period for the analytes of interest. Dialyzed hearts demonstrated improved bioenergetics as evidenced by accelerated purine metabolism and less pronounced accumulation of intermediates of fatty acid β/ω-oxidation. Metabolic waste accumulation such as pro-inflammatory lipid mediators (e.g., leukotrienes) was mitigated thereby supporting the process of resolution of inflammation through excretion of specialized pro-resolving mediators (resolvins D1/D2, E2, protecin D1).

SIGNIFICANCE: Through implementing the unique analytical pipeline we demonstrated that the addition of dialysis may preserve cardiac metabolism allowing for prolonged ESHP. This strategy has the potential to facilitate high-risk donor organs' reconditioning prior to transplantation.

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