Purpose: The INSPIRE trial revealed significant reduction of PGD grade 3, i.e. less ischemia reperfusion injury (IRI) using the Organ Care System (OCS) compared to controls for lung preservation. In order to investigate endothelial mechanisms initiated by cold vs. normothermic preservation, blood and perfusates of INSPIRE patients were assessed for proteins involved in endothelial integrity. We hypothesized that OCS preservation also supports endothelial integrity in parallel to an anti-inflammatory milieu.
Methods: Blood plasma pre, T0, T24 post Tx and perfusion solutions from 33 OCS and 26 SOC patients with control-preserved lungs were analysed for 100 cytokines, angiogenic factors, etc. by multiplex assays. Donor and recipient demographics, cold ischemic times and PGD scores were assessed and correlated with protein levels.
Results: Clinical evaluation (OCS/control) revealed mean recipient age: 50 vs. 49 years, diagnosis: idiopathic fibrosis (n=17/10), cystic fibrosis (n=7/8), idiopathic pulmonary hypertension (n=3/3) and emphysema (n=6/5), mean total cold ischemic times (CIT) 258±6 vs. 549±22 min (p<0.0001). In the OCS group, no cumulative PGD score > 2 was observed compared to 19% PGD3 in SOC (p=0.035). Less IRI in OCS patients was shown by significantly reduced IL-6, CXCL8, CXCL10, CCL2 plasma levels at T0. OCS plasma levels at T0 were also significantly lower for sCD31 (p=0.002), ICAM-1 (p=0.025), PAI-1 (p=0.03), leading to a higher PAI-1/uPA ratio of 82 in OCS compared to 67 in SOC. Lower VCAM-1, IGFBP-1, Ang-2, uPA, sHer2/neu, sVEGFR2 levels were detected in OCS compared to SOC recipients but did not reach statistical significance. Plasma levels of endoglin (CD105, p=0.01), PlGF (p=0.02) correlated with CIT. In contrast to the PGD correlation to IL-6 in SOC patients, none of these proteins showed a PGD correlation at T0 or T24. In contrast to plasma, significantly higher concentrations of these proteins were measured in OCS vs. SOC perfusates (p<0.01).   
Conclusion: During normothermic lung preservation using the OCS system, reduced IRI is accompanied with protection of the endothelium, which can be detected by lower T0 plasma levels of endothelial activation markers. Thus, lung preservation using the OCS initiates an anti-inflammatory cascade and a tissue-protective milieu resulting in improved graft function.