Lung Ischemia-Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?

Lung ischemia-reperfusion injury (LIRI) remains a major contributor to perioperative morbidity and mortality in thoracic surgery, especially for lung transplantations, where it is one of the principal drivers of primary graft dysfunction (PGD). Although substantial advances have been made in surgical technique, donor management, and perioperative care, LIRI continues to pose a significant clinical challenge. Mechanistically, LIRI reflects a combined pathology of oxidative stress, endothelial and glycocalyx disruption, innate immune activation, mitochondrial dysfunction, and regulated cell death, resulting in loss of alveolar-capillary barrier integrity and gas exchange failure. Current management is phase-specific and multimodal, spanning donor care and preservation, controlled reperfusion and lung-protective ventilation, and pharmacological treatments. Treatment candidates that target oxidative stress and inflammatory cascades (e.g., antioxidants, complement and adenosine pathways, mesenchymal stromal cell products, and dipeptidyl-peptidase-4 inhibition) show promise, yet translation into a clinical scenario remains difficult. Increasing evidence supports endothelial-preserving and mitochondria-sparing strategies, rigorous perioperative bundles, and biomarker-guided trials to move from pathophysiology to practice. Ultimately, addressing LIRI requires an integrated, multidisciplinary approach that spans surgical, anesthetic, and pharmacologic domains, with the goal of improving both early outcomes and long-term graft survival in lung transplant patients.