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Updated: Jul 22, 2026
Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism
Published on: January 12, 2019
Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex
Lars Saemann1,2, Kristin Wächter1, Adrian-Iustin Georgevici1,3
1Department of Cardiac Surgery, University Hospital Halle (Saale), University of Halle, 06120 Halle (Saale), Germany.
Insights
Hypothermic crystalloid perfusion (HCP) shows promise for reconditioning donation after circulatory death (DCD) hearts, reducing inflammation and improving gene expression compared to normothermic blood perfusion (NBP). This study investigated transcriptomic changes in DCD hearts under different perfusion methods.
Area of Science:
- Cardiovascular Research
- Organ Transplantation
- Molecular Biology
Background:
- Donation after circulatory death (DCD) hearts are typically preserved using normothermic blood perfusion (NBP).
- Hypothermic crystalloid perfusion (HCP) has demonstrated superior reconditioning of left ventricular (LV) contractility.
- Transcriptomic alterations in DCD hearts following HCP and NBP remain largely uncharacterized.
Purpose of the Study:
- To investigate transcriptomic changes in the myocardium and coronary arteries of DCD hearts.
- To compare the effects of HCP versus NBP on gene expression profiles.
- To identify key genes associated with different perfusion strategies in DCD hearts.
Main Methods:
- Utilized a porcine model with DCD hearts subjected to NBP or HCP (oxygenated HTK solution) for 4 hours, followed by 2 hours of reperfusion.
- Included a DCD group (immediate reperfusion) and a control group (no circulatory death).
- Performed transcriptomics on LV myocardial and LAD samples using microarrays, analyzing 25,470 genes and employing the Boruta algorithm for gene selection.
Main Results:
- NBP led to significant gene regulation in LAD (1915 genes) and minor regulation in myocardium (6 genes), associated with mitochondrial calcium, ROS production, reduced endothelial sprouting, and inflammation.
- HCP resulted in differential gene regulation: 259 downregulated and 52 upregulated in myocardium; 27 downregulated and 765 upregulated in LAD.
- Seven key genes (ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, IL-6) were identified for group differentiation. HCP downregulated genes linked to NF-κB, STAT3, SASP activation, and inflammation.
Conclusions:
- HCP demonstrates a more favorable transcriptomic profile in DCD hearts compared to NBP, indicated by reduced inflammatory gene expression.
- NBP is associated with increased oxidative stress and inflammatory pathways, potentially impairing heart recovery.
- Transcriptomic analysis provides valuable insights into the molecular mechanisms underlying different perfusion strategies for DCD heart preservation.
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.
