Metabolic changes during cold ischemic preservation and reperfusion in porcine lung transplants

Abstract

Lung transplantation is a cornerstone in treating patients with end-stage lung disease, yet ischemia-reperfusion injury poses significant complications in posttransplant recovery. This study aimed to understand the effects of donor type, cold ischemic time (CIT), and reperfusion on metabolic changes in lung grafts. Porcine donor lungs underwent different CITs on ice: minimal time (control), 6 hours (CIT-6H), and 30 hours (CIT-30H). Additionally, lungs recovered from animals after brain death (BD) underwent 24-hour CIT (BD-CIT-24H). Both CIT-30H and BD-CIT-24H lungs underwent ex vivo lung perfusion for 12 hours, followed by left lung transplantation and reperfusion for 2 hours. Lung tissue samples were subjected to metabolomic analysis. Cold preservation induced time-dependent changes of certain metabolites. In the BD-CIT-24H group, while most trends in metabolite levels were similar to those in the CIT-30H group, some were markedly different. In CIT-30H lungs, reperfusion induced significant changes in the carbohydrate and amino acid pathways, along with consumption of energy substrates and reduction in antioxidants. BD donor lungs exhibited significantly reduction in lysophospholipids after reperfusion. Understanding these metabolic changes in the lung grafts shed lights on the mechanism of ischemia-reperfusion injury, offering valuable insights for future development of targeted strategies to improve donor lung preservation and clinical outcome.