Sequential Ex Vivo Lung Perfusion for Prolonged Lung Preservation: Does the Second EVLP Reset the Lung Conditions?

Abstract

<h3>Purpose</h3> Ex vivo lung perfusion (EVLP) has the potential to expand the donor pool for lung transplantation by extending preservation times significantly beyond cold static preservation. We hypothesized that performing sequential EVLP would extend donor lung preservation time. <h3>Methods</h3> Ten lungs from Yorkshire pigs were procured in a standard fashion and randomized to 2 groups. Control lungs (n=5) underwent 16 hrs of cold ischemic time (CIT) and 2 hrs EVLP (EVLP). Sequential EVLP lungs (n = 5) underwent 4 hrs of CIT (CIT1), 2 hrs EVLP (EVLP1), 10 hrs of CIT (CIT2), then 2 hrs EVLP (EVLP2) (<b>Figure A</b>). Transplant suitability was assessed based on physiological parameters at 2 hrs in cellular EVLP. Lungs were evaluated using lung weight (LW), ultrasound, ATP levels, histology, and electron microscopy. <h3>Results</h3> EVLP2 had significantly higher PaO₂/FiO₂, lower shunt fraction, and A-a gradient compared to Control (p = 0.02, each, <b>Figure B</b>). LW ratio (LW 2 hrs / 0 hr) was significantly lower in EVLP2 vs. Control (p = 0.02, <b>Figure C</b>). Moreover, ultrasound score in whole lung and lower lobe to assess extravascular lung water was significantly lower in EVLP2 vs. Control (p = 0.04, p = 0.02, respectively, <b>Figure C</b>). ATP levels were significantly higher in EVLP2 vs. Control (p = 0.01). Histologic analysis of lungs in EVLP2 showed significantly reduced intra-alveolar edema, while there was no difference between groups in lung injury score. Electron microscopy demonstrated better preservation of endothelial cells and mitochondria in alveolar cells in EVLP2 lungs vs. Control. <h3>Conclusion</h3> Treating donor lungs with sequential EVLP resulted in superior oxygenation vs. lungs subjected to cold storage and 1 session of EVLP. Sequential EVLP was also associated with decreased LW ratio, lung edema, and higher ATP levels, in addition to favorable histology and electron microscopic findings. These suggest that sequential EVLP can have a potential role in prolonging lung preservation time.