Ex-Vivo Lung Perfusion Improves the Inflammatory Signalling Profile of the Porcine Donor Lung Following Transplantation

Stone JP, Ball AL, Crichley W, Yonan N, Liao Q, Sjöberg T, Steen S, Fildes JE.  

Transplantation. 2020 Jun 2. doi: 10.1097/TP.0000000000003338. Online ahead of print. Transplantation. 2020.PMID: 32502131

Background:
Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs prior to transplantation may improve outcomes. Evidence exists that ex-vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear. This study aimed to characterise the inflammatory signalling profile of the lung following standard and EVLP transplant and delineate the immediate impact on the recipient circulation.

Methods:
Female recipient pigs (n=12) were randomised to undergo left lung transplantation from male donors either using the gold standard protocol (static cold storage) or following 3 hours of EVLP. The relative phosphorylation of 44 phosphokinases and the relative expression of 35 apoptosis related molecules were profiled within the donor lung 24 hours post-transplantation.

Results:
A global profile of mitochondrial salvage and cell survival was observed in the EVLP lung tissue compared to lungs undergoing standard transplantation. This included increased phosphorylation of downstream pro-signalling kinases, including ERK1/2 and FAK. In addition, there was up-regulated expression of the anti-apoptotic proteins BCL-2, HSP-70, LIVIN and PON2 with down-regulation of apoptosis inducing mitochondrial associated molecules, including clusterin, cytochrome C and HTRA2/Omi. In the early post-operative period, there were significantly lower levels of circulating mitochondrial DNA in recipients receiving EVLP lungs compared to a standard transplant (p=0.016). Genomic DNA did not differ between groups, with donor DNA undetectable at all time-points.

Conclusion:
EVLP alters the inflammatory signalling profile of the donor lung prior to transplantation, with a global cell survival and anti-apoptotic signature.