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Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction
Lars Saemann1,2, Fabio Hoorn2,3, Adrian-Iustin Georgevici1,4
1Department of Cardiac Surgery, University Hospital Halle, University of Halle, Ernst Grube Straße 40, 06120 Halle, Germany.
Insights
Cytokine adsorption during blood perfusion in hearts from circulatory death donors prevented microvascular dysfunction. This method preserved endothelial function and reduced oxidative stress, offering a promising strategy for heart transplantation.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Organ Preservation
Background:
- Microvascular dysfunction (MVD) impairs cardiac allograft function, often exacerbated by ischemia/reperfusion injury (IRI).
- Hearts from circulatory death (DCD) donors face warm ischemia before ex vivo perfusion, posing challenges for endothelial health.
- The efficacy of cytokine adsorption during perfusion to mitigate MVD in DCD hearts remains uninvestigated.
Purpose of the Study:
- To evaluate the impact of cytokine adsorption during ex vivo blood perfusion (BP) on preventing microvascular dysfunction in porcine DCD hearts.
- To assess microvascular autoregulation, endothelial injury markers, and gene expression profiles following cytokine adsorption during BP.
Main Methods:
- A porcine DCD model was used, comparing hearts undergoing BP with (DCD-BP^CytoS) or without (DCD-BP) cytokine adsorption (CytoSorb®).
- Microvascular function was assessed via coronary perfusion pressure and Laser-Doppler-Perfusion (LDP).
- Immunoreactivity for oxidative stress markers (nitrotyrosine, HNE), endothelial markers (CD54, CD106, CD31, eNOS), and cytokine profiles were analyzed. Gene expression was profiled and analyzed using machine learning.
Main Results:
- Relative myocardial microcirculation (LDP) was significantly improved in the DCD-BP^CytoS group compared to DCD-BP.
- Pro- and anti-inflammatory cytokines were reduced, while eNOS expression increased in the DCD-BP^CytoS group.
- Markers of endothelial injury (nitrotyrosine, HNE, CD54, CD106, CD31) were significantly decreased, indicating preserved endothelial integrity.
Conclusions:
- Cytokine adsorption during ex vivo blood perfusion effectively counteracts microvascular dysfunction in DCD hearts.
- This approach preserves microvascular endothelium by mitigating oxidative stress and IRI in coronary arterioles.
- The findings suggest a promising strategy to improve the viability and function of DCD cardiac allografts.
Abstract:
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-BPCytoS, n = 5) or without (DCD-BP, n = 5) cytokine adsorption (CytoSorb®). 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-BPCytoS group (1.51 ± 0.17 vs. 1.08 ± 0.17). Several pro- and anti-inflammatory cytokines were reduced in the DCD-BPCytoS 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-BPCytoS group. Three genes allowed exact differentiation between groups; regulation of HIF1A enabled differentiation between perfusion (DCD-BP, DCD-BPCytoS) and non-perfusion groups. CAV1 allowed differentiation between BP and BPCytoS. 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.
