Cytokine Adsorption During Ex Vivo Blood Perfusion Improves Contractility of Donation After Circulatory Death Hearts

Lars Saemann; Sabine Pohl; Kristin Wächter; Adrian-Iustin Georgevici; Conny Köhler; Jennifer Jünger; Fabio Hoorn; Nitin Gharpure; Anne Großkopf; Sevil Korkmaz-Icöz; Folker Wenzel; Matthias Karck; Andreas Simm; Gábor Szabó

doi:10.1161/JAHA.124.036872

Cytokine Adsorption During Ex Vivo Blood Perfusion Improves Contractility of Donation After Circulatory Death Hearts

J Am Heart Assoc. 2024 Nov 22:e036872. doi: 10.1161/JAHA.124.036872. Online ahead of print.

Authors

Lars Saemann^{1

2}, Sabine Pohl¹, Kristin Wächter¹, Adrian-Iustin Georgevici^{1

3}, Conny Köhler¹, Jennifer Jünger¹, Fabio Hoorn², Nitin Gharpure¹, Anne Großkopf¹, Sevil Korkmaz-Icöz^{1

2}, Folker Wenzel⁴, Matthias Karck², Andreas Simm¹, Gábor Szabó^{1

2}

Affiliations

¹ Department of Cardiac Surgery University Hospital Halle (Saale), University of Halle Halle Germany.
² Department of Cardiac Surgery University Hospital Heidelberg Heidelberg Germany.
³ Department of Anaesthesiology, St. Josef Hospital Ruhr-University Bochum Bochum Germany.
⁴ Faculty Medical and Life Sciences Furtwangen University Villingen-Schwenningen Germany.

PMID: 39575707
DOI: 10.1161/JAHA.124.036872

Abstract

Background: Donation after circulatory death (DCD) hearts have to withstand ischemia/reperfusion injury that is partially driven by proinflammatory cytokines and decreases ventricular contractility. We hypothesize that cytokine adsorption during normothermic ex vivo blood perfusion of DCD hearts reduces the cytokine levels and improves ventricular contractility.

Methods and results: Porcine DCD hearts were maintained 4 hours by ex vivo blood perfusion with (DCD-BP^CytoS, all groups: N=8) or without (DCD-BP) CytoSorb, followed by 2 hours reperfusion with fresh blood, including left ventricular functional analysis using a balloon catheter. In a control and a DCD group, hearts were evaluated after procurement. We determined lactate and cytokines after ex vivo blood perfusion and the myocardial and left anterior descending artery transcriptome using microarrays after reperfusion. In DCD-BP^CytoS, the developed pressure (control: 124±7 mm Hg/s, DCD: 86±4 mm Hg/s, DCD-BP: 69±11 mm Hg/s, DCD-BP^CytoS: 112±9 mm Hg/s; P<0.05) and maximal slope of pressure increment (control: 2010±39 mm Hg/s, DCD: 1219±164 mm Hg/s, DCD-BP: 964±163 mm Hg/s, DCD-BP^CytoS: 1794±205 mm Hg/s; P<0.05) were higher compared with DCD-BP and DCD hearts. However, contractility decreased later during reperfusion without CytoSorb. After 4 hours, troponin, lactate (45±5% versus 69±9%, P<0.05), IL (interleukin)-1β, -1ra, and -8 were lower in DCD-BP^CytoS hearts. In the myocardium of DCD-BP^CytoS compared with DCD-BP hearts, inflammatory mediator receptor activity/binding pathways were enriched, and pathways for collagen-containing extracellular matrix and contractile fiber were underrepresented. In the left anterior descending artery of DCD-BP^CytoS hearts, serine/threonine/tyrosine kinase activity and wound-healing pathways were enriched, and mitochondrial protein-containing complex and respiratome-associated pathways were underrepresented.

Conclusions: CytoSorb during ex vivo blood perfusion enhances the maintenance of DCD hearts and is likely to improve graft function after transplantation.

Keywords: CytoSorb; cytokine adsorption; cytokines; donation after circulatory death; heart transplantation; machine perfusion.