AUTHOR=Radomsky Lena , Koch Achim , Olbertz Carolin , Liu Yongjie , Beushausen Kerstin , Keil Jana , Rauen Ursula , Falk Christine S. , Kühne Jenny F. , Kamler Markus 

TITLE=Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1245618

DOI=10.3389/fcvm.2023.1245618

ISSN=2297-055X

ABSTRACT=Background: Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, especially for marginal donor lungs after donation after circulatory death (DCD). Despite major efforts, the optimal perfusion protocol as well as composition of the perfusate in clinical LTX has not been identified. The aim of our study was to compare cytokine/chemokine concentrations in different perfusion solutions during EVLP, starting after one or nine hours cold static preservation (CSP) in a porcine cardiac arrest model and to correlate inflammatory parameters to oxygenation capacities.Methods: Following cardiac arrest, lungs were harvested and groups processed as immediate (I-EVLP) and delayed EVLP (D-EVLP) after one and nine hours of CSP, respectively. D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing dextran (CD) or dextran/albumin (CDA). Cytokine/chemokine levels were analyzed at baseline (0h), after 1h and 4h EVLP using Luminex-based multiplex assays. This is a provisional file, not the final typeset article Results: Within 4h EVLP, concentrations of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α and IL-1β increased significantly (p<0.05) in all experimental groups. CD solution contained lower levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, IL-18 (p<0.05) compared to Steen solution samples. Concentrations of all experimental groups correlated negatively with oxygenation capacity-values (p<0.05). Protein concentrations did not reach statistical significance for I-vs. D-EVLP and CD-vs. CDA-solutions.In a porcine cardiac arrest model, longer CSP prior to EVLP did not result in enhanced protein secretion into perfusates. CD solution dampened the cytokine/chemokine secretion most likely by iron chelators and/or protecting effects of dextran. Supplementation with albumin did not lead to a further reduction of cytokine/chemokine secretion into perfusates. These findings may help to optimize the preservation procedure thereby enlarging the pool of donor organs.