Arnold, Maria;
Do, Peter;
Davidson, Sean M;
Large, Stephen R;
Helmer, Anja;
Beer, Georgia;
Siepe, Matthias;
(2024)
Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation.
International Journal of Molecular Sciences
, 25
(8)
, Article 4153. 10.3390/ijms25084153.
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Abstract
Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.
| Type: | Article |
|---|---|
| Title: | Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/ijms25084153 |
| Publisher version: | https://doi.org/10.3390/ijms25084153 |
| Language: | English |
| Additional information: | © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). |
| Keywords: | heart transplantation; donation after circulatory death; cardiac energy metabolism; warm ischemia; ischemia–reperfusion injury; ex situ heart perfusion; ex vivo heart perfusion; cardioprotection; reperfusion therapies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10192526 |
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