Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation

TLDR

Ex vivo treatment of injured donor lungs may accelerate recovery and reduce reperfusion injury, potentially improving lung transplantation outcomes. The study aimed to assess how prolonged normothermic ex vivo lung perfusion affects ischemic injury. Pig donor lungs were cold‑preserved for 12 h, then either kept static or perfused normothermically for another 12 h before transplantation and 4‑h reperfusion, with tight‑junction integrity evaluated by ZO‑1 staining. Normothermic perfusion improved oxygenation, reduced edema, preserved barrier integrity, and attenuated reperfusion injury, thereby accelerating lung recovery compared to cold preservation.

Abstract

Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation. We have recently demonstrated a feasible technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37 degrees C with Steen solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO(2) 531 +/- 43 vs. 244 +/- 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens-1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery.