Successful 3-day lung preservation using a cyclic normothermic ex vivo lung perfusion strategy

Background Cold static preservation (CSP) at higher temperatures (10 degrees C) has been recently shown as an optimal strategy up to 24-36h of preservation. Here, we hypothesized that alternating 10 degrees C static storage with cycles of normothermic ex vivo lung perfusion (EVLP) would provide conditions for cellular recharge, allowing for multi-day lung preservation. Methods Donor lungs from male Yorkshire pigs were preserved using 10 degrees C CSP with two cycles of 4h EVLP. After a total of 3 days of preservation, a left lung transplant was performed followed by 4h of graft evaluation. As controls, 2 lungs were preserved solely with continuous 10 degrees C preservation for 3 days and transplanted. Findings For animals receiving lungs preserved using a cyclic EVLP protocol, lung function and histological structures were stable and the recipient systemic partial pressure of oxygen/fraction of inspired oxygen (P/F Ratio) after excluding the contralateral lung was 422 +/- 61 mmHg. In contrast, lungs preserved solely in continuous cold static storage at 10 degrees C for 72h developed massive lung failure, resulting in recipient death. Metabolomic analysis revealed that EVLP plays a critical role in the re-vitalization of key central carbon energy metabolites (Glucose, Succinate, N-Acetyl Aspartate) and reducing the expression of the inflammasome activation marker CASP1. Interpretation In conclusion, we demonstrate for the first time the feasibility of 3-day lung preservation leading to excellent early post-transplant outcomes. The thoughtful combination of cold storage (10 degrees C) and intermittent EVLP can open new opportunities in organ transplantation. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.