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Review
. 2023 Nov 24;24(23):16693.
doi: 10.3390/ijms242316693.

Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion

Dimitris Kounatidis  1 , Vassiliki Brozou  1 , Dimitris Anagnostopoulos  1 , Constantinos Pantos  1 , Athanasios Lourbopoulos  1 , Iordanis Mourouzis  1
Affiliations
Review

Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion

Dimitris Kounatidis et al. Int J Mol Sci. .

Abstract

Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.

Keywords: Organ Care System; cardioplegia; heart transplantation; hypothermic machine perfusion; kinases; normothermic machine perfusion; static cold storage; thyroid hormone.

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Conflict of interest statement

The following patent is relevant to the work in this manuscript: PCT/4972/2021. Pharmaceutical composition comprising L-triiodothyronine (T3) for use in the treatment of tissue hypoxia and sepsis. CP and IM are the inventors and hold royalties in relation to this patent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pathophysiological mechanisms of thyroid hormone (TH) action in normothermic machine perfusion. Abbreviations: p38/MAPK: p38/mitogen-activated protein kinase; IL-6: interleukin-6; c-Jun: c-Jun peptide; JNKs: c-Jun n-terminal kinases; Bcl-2: B-cell lymphoma-2 protein family; TR: thyroid receptor; HIF: hypoxia-inducible factor-1α; NO: nitric oxide; PI3K/Akt: phosphatidylinositol 3-kinase/protein kinase B; P: phosphorylation; eNOS: Endothelial nitric oxide synthase; PGC-1α; peroxisome proliferator-activated receptor-gamma coactivator-1alpha; AMPK: adenosine monophosphate-activated protein kinase.
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This research received no external funding.