Alpha-1-Antitrypsin Treatment during Ex Vivo Lung Perfusion Improves Function of Severely Injured Human Lungs

Clinical application of ex vivo lung perfusion (EVLP) has increased donor lung utilization through functional assessment. EVLP is a possible platform for donor lung repair and reconditioning. Alpha-1-antitrypsin (A1AT) is a serine protease inhibitor with anti-inflammatory properties. We investigated its effects on eight human lungs declined for clinical transplantation during EVLP. Each lung was separated into left and right lungs and assigned randomly to receive A1AT or as control. During 12h EVLP, lung function, cytokines and soluble adhesion molecules in the perfusate were measured. Perfusate loss was recorded. Zonula occludens protein-1 (ZO-1) in lung tissue was evaluated using immunofluorescent staining. A1AT-treated lungs demonstrated significantly improved function with higher oxygenation and lung compliances. Notably, perfusate loss and wet to dry weight ratio were significantly lower in the A1AT group. A1AT treatment led to decreased levels of inflammatory mediators (ET-1, CCL2, and MMP3), and increased expression of ZO-1, indicating enhanced tight junction integrity. A1AT treatment during EVLP enhanced lung function, reduced vascular permeability and inflammatory response in severely injured human lungs. Clinical application of A1AT during EVLP may improve donor lung quality, increase donor lung utilization and prevent ischemia reperfusion injury in lung transplantation.