Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion
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Published:2024-01-19
Issue:2
Volume:25
Page:1261
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Saemann Lars12ORCID, Wächter Kristin1, Georgevici Adrian-Iustin13, Pohl Sabine1, Hoorn Fabio2, Veres Gábor12, Korkmaz-Icöz Sevil12, Karck Matthias2, Simm Andreas1ORCID, Szabó Gábor12
Affiliation:
1. Department of Cardiac Surgery, University Hospital Halle (Saale), University of Halle, 06120 Halle (Saale), Germany 2. Department of Cardiac Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany 3. Department of Anaesthesiology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
Abstract
Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine–tryptophane–ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.
Funder
Open Access Publication Fund of the Martin-Luther-University Halle-Wittenberg European Union State of Saxony-Anhalt, Germany German Research Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference16 articles.
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