Biomarkers of standard criteria and marginal donor lungs during ex vivo lung perfusion: A comparative study

Ex vivo lung perfusion (EVLP) is a well-established method for assessing and reconditioning donor lungs before lung transplantation (LTx). Remarkably, clinical outcomes between standard criteria and marginal donor lungs after EVLP are similar despite differences in lung quality. Therefore, we explored several biomarkers during EVLP in this study. Novel findings could guide future interventions to enhance lung quality and expand the donor pool.

EVLP was performed for ≥180 min with 18 standard criteria (logistical) and 15 marginal donor lungs. The biomarkers were measured in the perfusate after 90 and 180 min: d-dimer, Prothrombin Fragment 1+2 (F1+2), Plasminogen Activator Inhibitor-1 (PAI-1), urokinase Plasminogen Activator Receptor (uPAR), IL-1β, IL-6, IL-8, TNF-α, syndecan-1, hyaluronan and Vascular Cell Adhesion Molecule-1 (VCAM-1).

In the logistical and marginal group, 16/18 and 12/15 were transplanted, respectively. All biomarkers increased significantly during EVLP. Remarkably, d-dimer, F1+2, uPAR, IL-6, IL-8, syndecan-1, hyaluronan, and VCAM-1 were significantly higher in the marginal group. Declined donor lungs had significantly higher levels of syndecan-1 and hyaluronan than all transplanted donor lungs. Lung function during EVLP and primary graft dysfunction (PGD) were similar between the transplanted standard and marginal lungs. No significant correlations with PGD were observed.

Marginal donor lungs sustained more injury as reflected in higher levels of fibrin degradation, inflammation, glycocalyx shedding, and endothelial activation. In addition, declined donor lungs exhibited significantly higher glycocalyx shedding. Therefore, both logistical and marginal donor lungs could potentially benefit from thrombolysis, inflammation-reducing therapy, and endothelial preservation during EVLP to enhance lung quality.