Post-Ex Vivo Lung Perfusion Hypothermic Storage Limits Inflammation and Endothelial Dysfunction

During an ex vivo lung perfusion (EVLP) procedure, the graft undergoes several temperature changes, transitioning from static storage (4°C) to warm reperfusion (37°C). These temperature variations could impact the graft and have never been explored. The objective of this study was to evaluate the impact of temperature changes on inflammation and endothelial dysfunction of the graft during an EVLP procedure.

A prospective, observational study.

A single university hospital.

Twenty consecutive donor lungs were assessed by EVLP.

Pro- and anti-inflammatory cytokines (interleukin [IL]-1β, IL-8, IL-6, tumor necrosis factor [TNF]-α, and IL-10), biomarkers of glycocalyx (heparan sulfate [HS], syndecan-1 [SD1]), and endothelial dysfunction (endothelin-1 [ET-1]) were measured at the declamping of the pulmonary artery of the first and the second implanted lung and at the end of EVLP. Associations between biomarker concentration variations and primary graft dysfunction were also assessed.

Compared to the first graft, IL-1β, IL-8, IL-6, and ET-1 concentrations remained similar, while IL-10 (p = 0.049) and TNF-α (p = 0.030) increased after post-EVLP hypothermic storage. Variations in IL-8 (R² = 0.56, p = 0.0062), TNF-α (R² = 0.61, p = 0.0039), and ET-1 (R² = 0.43, p = 0.01) during this period were positively associated with grade 3 primary graft dysfunction at 72 hours. EVLP significantly elevated IL-1β (p = 0.037), IL-6 (p = 0.0009), IL-8 (p < 0.0001), IL-10 (p < 0.0001), TNF-α (p < 0.0001), and ET-1 (p = 0.01), while HS and SD-1 were undetected.

Our findings suggest that post-EVLP hypothermic storage may contribute to mitigating inflammatory responses and endothelial dysfunction prior to transplantation. However, as several observed differences did not reach statistical significance, the results should be interpreted with caution. Further studies are needed to confirm these findings. Clinical Trials Registration Number NCT03987113, Principal investigator: Pr. Morgan LE GUEN.