Objectives

The INSPIRE trial revealed significant reduction of PGD grade 3 using the Organ Care System (OCS) compared to the standard of care (SOC) for lung preservation. In order to investigate immunological mechanisms initiated by cold vs. normothermic preservation, blood and perfusate samples were assessed for proteins involved in epi- and endothelial integrity and immune responses. We hypothesized that OCS preservation supports tissue integrity and anti-inflammatory milieu.

Methods

Blood plasma and perfusion solutions from 33 patients with OCS and 26 patients with SOC-preserved lungs were analysed for 95 plasma proteins by multiplex assays. Donor, recipient demographics, cold ischemic times (CIT), PGD scores at T0, T24 were assessed and correlated with protein levels.

Results

Clinical evaluation (OCS/SOC) revealed mean recipient age of 50/49y, diagnoses: idiopathic fibrosis (n=17/10), cystic fibrosis (n=7/8), idiopathic pulmonary hypertension (n=3/3), emphysema (n=6/5), mean total cold ischemic times (549±22 / 258±6 min p<0.0001). In the OCS group, no cumulative PGD score >2 was observed compared to 19% PGD3 in SOC (p=0.035). IL-6, CXCL8-10, CCL2, sICAM-1 plasma levels at T0 were significantly reduced in OCS patients (all p<0.01). Significantly higher levels of these factors were observed in OCS vs. SOC perfusates (all p< 0.001). IL-6 plasma levels at T0 in SOC recipients showed the strongest correlation to CIT (p=0.031), PaO2/FiO2 ratio (p=0.092) and PGD score >2 at T0 (p<0.05), T24 (p<0.05). We proposed a new mechanism of modulating IRI by induction of cytokine antagonists. Indeed, IL-1RA was significantly higher in OCS vs. SOC perfusates. In addition, IL-31 was highly correlated with IFN-g (p=0.001) in OCS, but absent in SOC perfusates.

Conclusion

Recipients of OCS-preserved lungs show significantly reduced IRI by reduced levels of pro-inflammatory factors, i.e. IL-6, CXCL8-10. The strong correlation of IL-6 with PGD score, PF and CIT in SOC but not OCS patients argues for a direct impact of inflammation on early graft function. As potential mechanism involved in reduction of IRI by OCS, we propose the induction of cytokine antagonists. Thus, portable EVLP may have the potential to ameliorate IRI and improve clinical outcome.

CITATION INFORMATION: Falk C, Wiegmann B, Neudörfl C, Kühn C, Tudorache I, Wvsar M, Haverich A, Warnecke G. Normothermic Donor Lung Preservation with Portable EVLP Significantly Reduces Ischemia/Reperfusion Injury in Lung Recipients by Promoting Cytokine Antagonists. Am J Transplant. 2017;17 (suppl 3).

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