Protective effects of hydrogen inhalation during the warm ischemia phase against lung ischemia-reperfusion injury in rat donors after cardiac death

Abstract

Background: Successful amelioration of long-term warm ischemia lung injury in donors after cardiac death (DCDs) can remarkably improve outcomes. Hydrogen gas provides potent anti-inflammatory and antioxidant effects against ischemia-reperfusion injury (IRI). This study observed the effects of hydrogen inhalation on lung grafts during the warm ischemia phase in cardiac death donors.

Methods: After cardiac death, rat donor lungs (n = 8) underwent mechanical ventilation with 40% oxygen plus 60% nitrogen (control group) or 3% hydrogen and 40% oxygen plus 57% nitrogen (hydrogen group) for 2 h during the warm ischemia phase in situ. Then, lung transplantation was performed after 2 h of cold storage and 3 h of recipient reperfusion prior to lung graft assessment. Rats that underwent left thoracotomy without transplantation served as the sham group (n = 8). The results of static compliance and arterial blood gas analysis were assessed in the recipients. The wet-to-dry weight ratio (W/D), inflammation, oxidative stress, cell apoptosis and histologic changes were evaluated after 3 h of reperfusion. Nuclear factor kappa B (NF-κB) protein expression in the graft was analyzed by Western blotting.

Results: Compared with the sham group, lung function, W/D, inflammatory reaction, oxidative stress and histological changes were decreased in both transplant groups (control and hydrogen groups). However, compared with the control group, exposure to 3% hydrogen significantly improved lung graft static compliance and oxygenation and remarkably decreased the wet-to-dry weight ratio, inflammatory reactions, and lipid peroxidation. Furthermore, hydrogen improved the lung graft histological changes, decreased the lung injury score and apoptotic index and reduced NF-κB nuclear accumulation in the lung grafts.

Conclusion: Lung inhalation with 3% hydrogen during the warm ischemia phase attenuated lung graft IRI via NF-κB-dependent anti-inflammatory and antioxidative effects in rat donors after cardiac death.

Keywords: Hydrogen; Ischemia-reperfusion injury; Warm ischemia phase.