Hydrogen Inhalation during Ex Vivo Lung Perfusion Ameliorates the Quality of Lung Grafts in Rats

Abstract

Purpose Hydrogen (H 2 ) has a high potential as a safe and multi-potent therapeutic gas. We have recently reported inhaled H 2 could prevent acute lung injury through anti-inflammatory and anti-apoptotic effects in lung injury animal models. We hypothesized that H 2 inhalation during ex-vivo lung perfusion (EVLP) that is a novel strategy for donor lung preservation, optimizes the opportunity and contributes to further refinement in the current EVLP strategy. Methods and Materials Using heart-lung blocks harvested from Lewis rats, our rat EVLP system was established in a stable and reliable fashion where rat lungs after 1hr cold preservation, perfused with acellular Steen solution and ventilated at 37°C on EVLP for 4hrs were evaluated. In the H 2 -treated group, lungs were ventilated with 2% H 2 during EVLP and their results were compared with those from lungs ventilated with air on EVLP as the control group. Results H 2 inhalation was associated with significantly better preserved graft function in terms of oxygenation, lung compliance and reduced pulmonary vascular resistance. In addition, H 2 -treated lungs exhibited significantly reduced proinflammatory cytokine (IL-6, IL-1β, TNF-α) mRNA levels in the allografts. Interestingly, H 2 -treated lungs resulted in significantly reduced elevation of lactate levels as well as hypoxia-inducible factor 1 (HIF-1) levels in lung tissues as compared to the control group, suggesting the contribution of H 2 to improve metabolism in lung grafts during EVLP. [ figure 1 ] Conclusions H 2 inhalation during EVLP may play a pivotal role in preserving better graft function through promotion of anti-inflammatory and cytoprotective effects as well as activation of mitochondrial biogenesis in lungs.