Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction
Microvascular dysfunction (MVD) in cardiac allografts is associated with an impaired endothelial function in the coronary microvasculature. Ischemia/reperfusion injury (IRI) deteriorates endothelial function. Hearts donated after circulatory death (DCD) are exposed to warm ischemia before initiating...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2280 |
| _version_ | 1797466022872088576 |
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| author | Lars Saemann Fabio Hoorn Adrian-Iustin Georgevici Sabine Pohl Sevil Korkmaz-Icöz Gábor Veres Yuxing Guo Matthias Karck Andreas Simm Folker Wenzel Gábor Szabó |
| author_facet | Lars Saemann Fabio Hoorn Adrian-Iustin Georgevici Sabine Pohl Sevil Korkmaz-Icöz Gábor Veres Yuxing Guo Matthias Karck Andreas Simm Folker Wenzel Gábor Szabó |
| author_sort | Lars Saemann |
| collection | DOAJ |
| description | Microvascular dysfunction (MVD) in cardiac allografts is associated with an impaired endothelial function in the coronary microvasculature. Ischemia/reperfusion injury (IRI) deteriorates endothelial function. Hearts donated after circulatory death (DCD) are exposed to warm ischemia before initiating ex vivo blood perfusion (BP). The impact of cytokine adsorption during BP to prevent MVD in DCD hearts is unknown. In a porcine DCD model, we assessed the microvascular function of hearts after BP with (DCD-BP<sup>CytoS</sup>, <i>n</i> = 5) or without (DCD-BP, <i>n</i> = 5) cytokine adsorption (CytoSorb<sup>®</sup>). Microvascular autoregulation was assessed by increasing the coronary perfusion pressure, while myocardial microcirculation was measured by Laser-Doppler-Perfusion (LDP). We analyzed the immunoreactivity of arteriolar oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal (HNE), endothelial injury indicating cell adhesion molecules CD54, CD106 and CD31, and eNOS. We profiled the concentration of 13 cytokines in the perfusate. The expression of 84 genes was determined and analyzed using machine learning and decision trees. Non-DCD hearts served as a control for the gene expression analysis. Compared to DCD-BP, relative LDP was improved in the DCD-BP<sup>CytoS</sup> group (1.51 ± 0.17 vs. 1.08 ± 0.17). Several pro- and anti-inflammatory cytokines were reduced in the DCD-BP<sup>CytoS</sup> group. The expression of eNOS significantly increased, and the expression of nitrotyrosine, HNE, CD54, CD106, and CD31, markers of endothelial injury, majorly decreased in the DCD-BP<sup>CytoS</sup> group. Three genes allowed exact differentiation between groups; regulation of HIF1A enabled differentiation between perfusion (DCD-BP, DCD-BP<sup>CytoS</sup>) and non-perfusion groups. CAV1 allowed differentiation between BP and BP<sup>CytoS</sup>. The use of a cytokine adsorption device during BP counteracts preload-dependent MVD and preserves the microvascular endothelium by preventing oxidative stress and IRI of coronary arterioles of DCD hearts. |
| first_indexed | 2024-03-09T18:30:56Z |
| format | Article |
| id | doaj.art-12aa984ac2a14dd1bba824f5d82b8d9a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T18:30:56Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-12aa984ac2a14dd1bba824f5d82b8d9a2023-11-24T07:32:39ZengMDPI AGAntioxidants2076-39212022-11-011111228010.3390/antiox11112280Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular DysfunctionLars Saemann0Fabio Hoorn1Adrian-Iustin Georgevici2Sabine Pohl3Sevil Korkmaz-Icöz4Gábor Veres5Yuxing Guo6Matthias Karck7Andreas Simm8Folker Wenzel9Gábor Szabó10Department of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyDepartment of Cardiac Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyFaculty Medical and Life Sciences, Furtwangen University, 78054 Villingen-Schwenningen, GermanyDepartment of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, GermanyMicrovascular dysfunction (MVD) in cardiac allografts is associated with an impaired endothelial function in the coronary microvasculature. Ischemia/reperfusion injury (IRI) deteriorates endothelial function. Hearts donated after circulatory death (DCD) are exposed to warm ischemia before initiating ex vivo blood perfusion (BP). The impact of cytokine adsorption during BP to prevent MVD in DCD hearts is unknown. In a porcine DCD model, we assessed the microvascular function of hearts after BP with (DCD-BP<sup>CytoS</sup>, <i>n</i> = 5) or without (DCD-BP, <i>n</i> = 5) cytokine adsorption (CytoSorb<sup>®</sup>). Microvascular autoregulation was assessed by increasing the coronary perfusion pressure, while myocardial microcirculation was measured by Laser-Doppler-Perfusion (LDP). We analyzed the immunoreactivity of arteriolar oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal (HNE), endothelial injury indicating cell adhesion molecules CD54, CD106 and CD31, and eNOS. We profiled the concentration of 13 cytokines in the perfusate. The expression of 84 genes was determined and analyzed using machine learning and decision trees. Non-DCD hearts served as a control for the gene expression analysis. Compared to DCD-BP, relative LDP was improved in the DCD-BP<sup>CytoS</sup> group (1.51 ± 0.17 vs. 1.08 ± 0.17). Several pro- and anti-inflammatory cytokines were reduced in the DCD-BP<sup>CytoS</sup> group. The expression of eNOS significantly increased, and the expression of nitrotyrosine, HNE, CD54, CD106, and CD31, markers of endothelial injury, majorly decreased in the DCD-BP<sup>CytoS</sup> group. Three genes allowed exact differentiation between groups; regulation of HIF1A enabled differentiation between perfusion (DCD-BP, DCD-BP<sup>CytoS</sup>) and non-perfusion groups. CAV1 allowed differentiation between BP and BP<sup>CytoS</sup>. The use of a cytokine adsorption device during BP counteracts preload-dependent MVD and preserves the microvascular endothelium by preventing oxidative stress and IRI of coronary arterioles of DCD hearts.https://www.mdpi.com/2076-3921/11/11/2280heart transplantationmicrovascular dysfunctionoxidative stressdonation after circulatory deathmachine perfusioncytokine adsorption |
| spellingShingle | Lars Saemann Fabio Hoorn Adrian-Iustin Georgevici Sabine Pohl Sevil Korkmaz-Icöz Gábor Veres Yuxing Guo Matthias Karck Andreas Simm Folker Wenzel Gábor Szabó Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction Antioxidants heart transplantation microvascular dysfunction oxidative stress donation after circulatory death machine perfusion cytokine adsorption |
| title | Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction |
| title_full | Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction |
| title_fullStr | Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction |
| title_full_unstemmed | Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction |
| title_short | Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction |
| title_sort | cytokine adsorber use during dcd heart perfusion counteracts coronary microvascular dysfunction |
| topic | heart transplantation microvascular dysfunction oxidative stress donation after circulatory death machine perfusion cytokine adsorption |
| url | https://www.mdpi.com/2076-3921/11/11/2280 |
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