Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD.

DCD heart transplantation NMR spectroscopy biomarkers cardiac graft evaluation ex-situ heart perfusion / ex-vivo heart perfusion / normothermic machine perfusion

Journal

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703

Informations de publication

Date de publication:
07 Sep 2024
Historique:
received: 02 05 2024
revised: 14 08 2024
accepted: 17 08 2024
medline: 10 9 2024
pubmed: 10 9 2024
entrez: 9 9 2024
Statut: aheadofprint

Résumé

Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. Circulating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min. In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

Sections du résumé

BACKGROUND BACKGROUND
Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality.
METHODS METHODS
Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy.
RESULTS RESULTS
Circulating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min.
CONCLUSIONS CONCLUSIONS
In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

Identifiants

DOI: 10.1016/j.healun.2024.08.016 PMID: 39251114
pubmed: 39251114
pii: S1053-2498(24)01805-9
doi: 10.1016/j.healun.2024.08.016
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Selianne Graf (S)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: selianne.graf@unibe.ch.

Manuel Egle (M)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: manuel.egle@unibe.ch.

Maria-Nieves Sanz (MN)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: nsanz32@gmail.com.

Adrian Segiser (A)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: adrian.segiser@unibe.ch.

Alexia Clavier (A)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: alexia.clavier@unibe.ch.

Maria Arnold (M)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: maria.arnold2@unibe.ch.

Didier Gsponer (D)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: didier_108@hotmail.com.

Maris Bartkevics (M)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland. Electronic address: maris.bartkevics@insel.ch.

Alexander Kadner (A)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland.

Matthias Siepe (M)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland. Electronic address: matthias.siepe@insel.ch.

Peter Vermathen (P)

Magnetic Resonance Methodology Group, Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland. Electronic address: peter.vermathen@insel.ch.

Sarah Longnus (S)

Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: sarah.henninglongnus@insel.ch.

Classifications MeSH