Progressive Hypoxia Enhances Lung Preservation via Oil Sealing

Lung transplantation remains a critical life-saving intervention for end-stage pulmonary diseases, yet optimal organ preservation between procurement and implantation poses a major limitation in clinical practice. While cold static preservation (CSP) at 4°C effectively reduces metabolic demand and delays ischemic damage, this conventional approach fails to adequately prevent cold ischemia-reperfusion injury (IRI) and ensuing primary graft dysfunction. Here we developed an elegant preservation strategy involving paraffin oil overlay of preservation solution, demonstrating significant preservation improvements in rat, porcine, and human lungs. Mechanistic studies revealed that this method progressively activates the hypoxia-inducible factor 1 alpha (HIF-1α) pathway, which reduces oxidative stress and inflammation and promotes metabolic reprogramming toward glycolysis and amino acid metabolism. This cost-effective modification of standard preservation protocol shows translational potential for extending donor lung viability and improving clinical transplantation outcomes.