Hydrogen gas inhalation during ex vivo lung perfusion of donor lungs recovered after cardiac death

Abstract

BACKGROUND: Ex vivo lung perfusion (EVLP) is a system that circulates normothermic perfusate into procured lungs, allowing for improved lung function and lung assessment. We investigated whether ventilation with hydrogen gas during EVLP improves the donation after cardiac death lung function and whether this effect persists after actual transplantation. METHODS: Ten pigs were randomly divided into a control group (n=5) and a hydrogen group (n=5). No treatment was administered to induce warm ischemic injury for 1 hour after cardiac arrest, and EVLP was applied in procured lungs for 4 hours. During EVLP, the control group was given room air for respiration, and the hydrogen group was given 2% hydrogen gas. After EVLP, the left lung graft was orthotopically transplanted into the recipient and reperfused for 3 hours. During EVLP and reperfusion, the functional parameters and arterial blood gas analysis (ABGA) were measured every hour. Superoxide dismutase, heme oxygenase, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and nucleotide-binding oligomerization domain-like receptor protein 3 were evaluated in lung tissue after reperfusion. Pathologic evaluations were performed, and the degree of apoptosis was evaluated. The wet/dry ratio was measured. RESULTS: During EVLP and reperfusion, functional parameters and ABGA results were better in the hydrogen group. The expressions of superoxide dismutase (p=0.022) and heme oxygenase-1 (p=0.047) were significantly higher in the hydrogen group. The expressions of IL-6 (p=0.024) and nucleotide-binding oligomerization domain-like receptor protein 3 (p=0.042) were higher in the control group, but IL-10 (p=0.037) was higher in the hydrogen group. The lung injury severity score and the number of apoptotic cells were higher and the degree of pulmonary edema was more severe in the control group than in the hydrogen group. CONCLUSIONS: Hydrogen gas inhalation during EVLP improved donation after cardiac death lung function via reduction of inflammation and apoptosis, and this effect persisted after LTx.