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

Selianne Graf; Manuel Egle; Maria-Nieves Sanz; Adrian Segiser; Alexia Clavier; Maria Arnold; Didier Gsponer; Maris Bartkevics; Alexander Kadner; Matthias Siepe; Peter Vermathen; Sarah Longnus

doi:10.1016/j.healun.2024.08.016

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

J Heart Lung Transplant. 2024 Sep 7:S1053-2498(24)01805-9. doi: 10.1016/j.healun.2024.08.016. Online ahead of print.

Authors

Affiliations

¹ 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.
² 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.
³ Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: nsanz32@gmail.com.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland. Electronic address: maris.bartkevics@insel.ch.
⁹ Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland.
¹⁰ Department of Cardiac Surgery, Inselspital, University of Bern, Bern, Switzerland. Electronic address: matthias.siepe@insel.ch.
¹¹ Magnetic Resonance Methodology Group, Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland. Electronic address: peter.vermathen@insel.ch.
¹² 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.

PMID: 39251114
DOI: 10.1016/j.healun.2024.08.016

Abstract

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: 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: 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: 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.

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