A novel modified Steen solution limits inflammatory processes during ex vivo lung perfusion and improves graft function post-transplantation

Abstract

BackgroundEx vivo lung perfusion allows donor lung preservation, assessment and reconditioning prior to transplantation, but is associated with increased inflammatory injury over time. Addition of anti-oxidative and anti-inflammatory agents to perfusate formulations could limit iatrogenic injury during perfusion. The effectiveness of a modified Steen solution containing acetyl salicylic acid, retinoic acid and methylprednisolone, was examined using a porcine extended criteria donor ex vivo lung perfusion and transplantation model. MethodsPorcine donor lungs underwent 24 hours cold storage and were then randomised to 4 hours normothermic ex vivo lung perfusion with modified Steen or original Steen, followed by single lung transplantation into a recipient pig. RNA-sequencing was used to assess tissue inflammatory changes during perfusion. Organ function was examined during perfusion and following transplantation and compared between groups. ResultsLungs perfused with modified Steen showed reduced pulmonary vascular resistance (p=0.0391) and stable pulmonary artery pressure despite achieving higher flows (p=0.0001) compared to Steen. Lung tissue showed negative enrichment of the TNF-α signalling via NF-κB pathway (p=0.0040) in modified Steen compared to Steen. Recipients of lungs perfused with modified Steen also showed improved post-transplantation oxygenation (p=0.0462). ConclusionsThis study highlights the superiority of modified Steen compared with original Steen. The modifications to Steen solution appear to limit inflammatory injury via the NF-κB signalling pathway during perfusion, leading to improved post-transplant function. Modified Steen provides the potential to improve post-transplant outcomes following EVLP of extended criteria lungs and could also facilitate extended assessment and preservation, as well as administration of advanced therapies.