Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase

Bin Zheng, Guangchao Zhang, Huacheng Zhou, Le Duan, Lini Quan, Mengdi Zhang, Zhe Li

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DOI: 10.1186/s12890-023-02504-6 DOI is the universal ID for this study.

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Background: Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism.

Methods: Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed.

Results: Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group. Conclusions: Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.

Publish Year 2023
Country China
Rank Positive
Journal BMC Pulmonary Medicine
Primary Topic Lung
Secondary TopicSurgery/Transplantation
Model Rat
Tertiary TopicTransplantation/Graft Injury
Vehicle Gas
pH N/A
Application Ventilation