Composition of Ex Vivo Lung Perfusion Solutions and Kinetics Define Differential Cytokine and Chemokine Secretion in a Porcine Cardiac Arrest Model of Lung Preservation

Purpose Ex vivo lung perfusion is an innovative technique to evaluate marginal lung organs especially after DCD. Normothermic continuous perfusion should reduce ischemic damage and improve the outcome of lung transplantation. However, the optimal protocol for EVLP has not been defined so far. The aim of our study was to compare cytokine/chemokine concentrations in perfusion solutions using different kinetics and solution compounds of EVLP in a porcine cardiac arrest model and to correlate the inflammatory parameters to oxygenation capacity values (∆pO2). Methods Following cardiac arrest and 1h of warm ischemia, lungs were harvested and flushed. Groups were processed as immediate (I-EVLP) 1h cold static preservation (CSP) and delayed (D-EVLP; 9h CSP). D-EVLP lungs were perfused with different solutions: Steen vs. modified Custodiol-N containing dextran (CD) or dextran/albumin (CDA). Cytokine/chemokine levels were analyzed at baseline (0h), after 1h, 4h using multiplex protein arrays. Results Concentrations of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α and IL-1β increased significantly (p Conclusion In a non-heart beating porcine cardiac arrest model with relevant IRI, lungs were perfused with normothermic EVLP. Longer CSP prior to EVLP did not result in enhanced cytokine secretion, but the first hours of reperfusion seem crucial for tissue damage. CD-solution dampens the cytokine/chemokine secretion probably by iron chelators and, possibly, protecting effects of dextran. Addition of albumin had no further effect on inflammation. Cytokine/chemokine concentrations correlated negatively with the oxygenation capacity, an important parameter for organ acceptance. These finding may help to optimize the ex vivo preservation procedure and possibly, more organs could reach the clinically relevant threshold for transplantation, thus, the pool of marginal donor lungs could be enlarged.