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Transcriptomic changes in the myocardium and coronary artery of donation after circulatory death hearts following ex vivo machine perfusion

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...

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Hauptverfasser: Saemann, Lars (VerfasserIn) , Wachter, Kristina (VerfasserIn) , Georgevici, Adrian-Iustin (VerfasserIn) , Pohl, Sabine (VerfasserIn) , Hoorn, Fabio (VerfasserIn) , Veres, Gábor (VerfasserIn) , Korkmaz-İçöz, Sevil (VerfasserIn) , Karck, Matthias (VerfasserIn) , Simm, Andreas (VerfasserIn) , Szabó, Gábor (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 January 2024
In: International journal of molecular sciences
Year: 2024, Jahrgang: 25, Heft: 2, Pages: 1-14
ISSN:1422-0067
DOI:10.3390/ijms25021261
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms25021261
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/25/2/1261
Volltext
Verfasserangaben:Lars Saemann, Kristin Wächter, Adrian-Iustin Georgevici, Sabine Pohl, Fabio Hoorn, Gábor Veres, Sevil Korkmaz-Icöz, Matthias Karck, Andreas Simm, Gábor Szabó
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 20.09.2024
Beschreibung:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms25021261

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