Lung inflation with hydrogen sulfide during the warm ischemia phase ameliorates injury in rat donor lungs via metabolic inhibition after cardiac death.

BACKGROUND

Hydrogen sulfide attenuates lung ischemia-reperfusion injury when inhaled or administered intraperitoneally. This study investigated the effects of lung inflation with HS during the warm ischemia phase on lung grafts from rat donors after cardiac death.

METHODS

One hour after cardiac death, donor lungs were inflated in situ for 2 h with either O or HS (O or HS group) during the warm ischemia phase or were deflated as a control procedure (n = 8). After 3 h of cold preservation, lung transplantation was performed. During the warm ischemia phase, the metabolism and mitochondrial structures of donor lungs were analyzed. Arterial blood gas analysis was performed on the recipients. Protein expression in the graft of nuclear factor E2-related factor (Nrf)2 and nuclear factor kappa B (NF-κB) was analyzed by Western blotting, and static compliance, inflammation, oxidative stress, and cell apoptosis were assessed after 3 h of reperfusion.

RESULTS

When the O and HS groups were compared with the control group, the mitochondrial structures were improved, and lactic acid levels, inflammation, oxidative stress, and cell apoptosis were significantly decreased; and glucose levels, as well as graft oxygenation and static compliance were increased. Simultaneously, the above indices showed further improvements, and the Nrf2 protein expression was significantly greater, and NF-κB protein expression was less in the HS group than the O group.

CONCLUSION

Lung inflation with HS during the warm ischemia phase inhibited metabolism in donor lungs via mitochondrial protection, attenuated graft ischemic-reperfusion injury, and improved graft function through NF-κB-dependent anti-inflammatory and Nrf2-dependent antioxidative and antiapoptotic effects.