In this animal (pig) study, the impact of cytokine adsorption during ex-vivo blood perfusion (BP) to prevent coronary microvascular dysfunction (CMVD) in hearts donated after circulatory death (DCD) was studied. DCD hearts were maintained for four hours by normothermic blood perfusion through the ascending aorta 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). Finally, the hearts of all groups underwent 60 min of perfusion with fresh blood to mimic the reperfusion effects after transplantation. The concentration of 13 cytokines were assessed in the perfusate and the expression of 84 genes was determined and analyzed using machine learning and decision trees. A further 5 non-DCD hearts served as a control for the gene expression analysis. Compared to DCD-BP, relative perfusion improved in the CytoSorb treated group (1.51 ± 0.17 vs. 1.08 ± 0.17), and several pro- and anti-inflammatory cytokines were reduced. The authors also demonstrated a reduced level of oxidative stress and an alleviated microvascular endothelial ischemia reperfusion injury in this group (DCD-BPCytoS). Regarding gene analysis, the expression of eNOS significantly increased, and the expression of nitrotyrosine, HNE, CD54, CD106, and CD31, all markers of endothelial injury, majorly decreased in the CytoSorb group. Three genes allowed exact differentiation between groups. The authors conclude that the use of cytokine adsorption during ex-vivo blood purification counteracts preload dependent microvascular dysfunction and preserves the microvascular endothelium by preventing oxidative stress and ischemic reperfusion injury of the coronary arterioles in circulatory death hearts. The findings suggest that the use of CytoSorb® in DCD hearts could be beneficial in the clinical setting.
Open-access publication: https://pubmed.ncbi.nlm.nih.gov/36421466/