Inhibition of Neutrophil Serine Proteases by Alpha 1 Antitrypsin in Perfadex Preserves Primary Graft Functions of Transplanted Murine Donor Lungs

Abstract

The risk of primary graft dysfunction (PGD) of donor lungs and early postoperative mortality after lung transplantation (LTx) increases with prolonged preservation times. PGD is triggered by early infiltrating neutrophils which release large amounts of elastase-related serine proteases and inflict irreversible damage on lung graft after cold ischemic storage. Cold ischemic storage for only 6 hours is generally accepted, when lungs are cooled down and preserved in Perfadex immediately after their removal from donors. The need of short preservation times reduces donor lung usage and narrows the geographical area of organ retrieval and transportation. We aimed to increase preservation times beyond 6 hours without impairing the early post-LTx outcome by adding alpha 1 antitrypsin (AAT), a serine-proteases inhibitor of human plasma, to the ice-cold storage solution. We hypothesized that AAT added to Perfadex would protect transplanted lungs against PGD and early graft failure by neutralizing serine proteases from activated neutrophils.