Optimal ex vivo lung perfusion techniques with oxygenated perfusate

Abstract

BACKGROUND: Accumulating evidence supports an increasing role of ex vivo lung perfusion (EVLP) in clinical lung transplantation. However, EVLP has adverse effects on the quality of lung grafts, which have rarely been discussed. Careful optimization of current EVLP protocols might improve outcomes. This study examined effects of different levels of oxygenation of the perfusate circulated through the lungs during EVLP and the impact on post-transplant functional outcomes. METHODS: We compared results of 4 different oxygenation levels in the perfusate during EVLP: 6% oxygen (O2), 40% O2, 60% O2, and 100% O2. We evaluated lung function, compliance, and vascular resistance and levels of glucose and other markers in the perfusate. After EVLP, lung grafts were transplanted, and post-transplant outcomes were compared. RESULTS: Lungs perfused with 40% O2 on EVLP had the lowest glucose consumption compared with the other perfusates. Lungs treated with 40% O2 or 60% O2 exhibited significantly less inflammation, as indicated by reduced pro-inflammatory cytokine messenger RNA levels compared with lungs perfused with 6% O2 or 100% O2. Significantly more oxidative damage was noted after 4 hours of EVLP perfused with 100% O2. After transplantation, lungs perfused with 40% O2 during EVLP had the best post-transplant functional outcomes. CONCLUSIONS: Optimization of O2 levels in the perfusate during EVLP improved outcomes in this rat model. Deoxygenated perfusate, the current standard during EVLP, exhibited significantly more inflammation with compromised cellular metabolic activity and compromised post-transplant outcomes.