Protein Expression Profiling Predicts Graft Performance in Clinical Ex Vivo Lung Perfusion

Abstract

Purpose To study the impact of normothermic ex vivo lung perfusion (EVLP) on cytokines, chemokines and growth factors and their correlation with graft performance either during perfusion or after implantation. Methods and Materials High-risk brain death donors and donors after cardiac death underwent 4-6 hours EVLP with intent to transplant. Using a multiplex magnetic bead array assay we evaluated multiple analytes in perfusate samples. Donor lungs were divided into three grous: I. Control: bilateral transplantation with good early outcome (absence of PGD grade 3); II. PGD3: bilateral lung transplantation with PGD grade 3 anytime within 72 hours; III. Declined: lungs rejected following EVLP. Single-lung transplants and patients bridged to LTx with extracorporeal life support were excluded. Results Of 36 cases included in this study, 17 were in group I, 6 in group II and 13 in group III. Of a total of 51 analytes, 30 were measurable in perfusates. While markers from samples at 1 hour had higher capacity for discrimination between groups I and III, at the end of EVLP there were more analytes significantly higher in group II compared to I. The best markers to differentiate declined lungs from controls lungs were IL-1ra (p=0.005, AUC 0.80) and SCGF-b (p Figure ) Conclusions Perfusate protein expression can differentiate lungs with good outcome from lungs with a poor outcome (PGD 3) after transplantation as well as lungs that were declined during EVLP.