Protective effects of hydrogen preconditioning in an ex vivo perfusion model on lung tissue from organ donation donors after cardiac death

  Objective  To investigate the protective effect of hydrogen preconditioning in an ex vivo perfusion model on lung tissue from organ donation donors after cardiac death (DCD).

  Methods  Eighteen New Zealand white rabbits were selected to construct ex vivo lung perfusion (EVLP) model. Air or air containing 2% hydrogen was used for ventilation, and arterial and airway pressure was monitored continuously. The infusion was sampled hourly to check for oxygenation. After EVLP, lung grafts were transplanted into large-eared rabbits of the same age in positive position, and lung function was examined.

  Results  There were statistically significant differences in oxygenation index[p_a(O₂)/FiO₂], pulmonary vascular resistance (PVR) and dynamic lung compliance between the two groups at 4 h after EVLP perfusion (P < 0.05). During EVLP, the mRNA expression levels of interleukin (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1 α (HIF-1α) in lung grafts in the hydrogen group were higher than those in the sham surgery group, but were lower than those in the control group (P < 0.05). Compared with 1, 2 and 3 h after EVLP perfusion, glucose consumption in both groups was decreased at 4 h (P < 0.05). The level of lactic acid in the control group at 4 h after EVLP was higher than that at 1, 2 and 3 h (P < 0.05). The lactic acid levels at 1, 2, 3 and 4 h in the hydrogen group were lower than those in the control group(P < 0.05). After EVLP for 4 h, the mitochondrial complex Ⅰ enzyme activity in the lung tissues of the control group and the hydrogen group was lower than that of the sham operation group, while the mitochondrial complex Ⅱ and Ⅳ activities and ATP levels in the hydrogen group were higher than those in the control group and the sham operation group (P < 0.05). During EVLP, the mRNA expression levels of heme oxygenase (HO) -1, peroxisome proliferator-activated receptor γ co-activator 1 (PGC-1) and nuclear respiratory factor-1 (NRF-1) in the hydrogen group were higher than those in control group and the sham operation group (P < 0.05).

  Conclusion  EVLP lung transplantation shows significant pro-inflammatory changes and impaired metabolic profile. Hydrogen pretreated lung graft can significantly reduce the proinflammatory reactions, promote the biogenesis of mitochondria in the lung during the whole process of lung transplantation, and play a better role in protecting the function of the transplanted lung.