Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats

Tomohiro Kawamura, Chien Sheng Huang, Naobumi Tochigi, Sungsoo Lee, Norihisa Shigemura, Timothy R. Billiar, Meinoshin Okumura, Atsunori Nakao*, Yoshiya Toyoda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


Background. Successful abrogation of ischemia/reperfusion (I/R) injury of lung grafts could significantly improve short- and long-term outcomes for lung transplant (LTx) recipients. Hydrogen gas has potent antioxidant and antiapoptotic properties and has been recently used in number of experimental and clinical studies. The purpose of this research was to investigate whether inhaled hydrogen gas could reduce graft I/R injury during lung transplantation. Methods. Orthotopic left LTxs were performed in syngenic Lewis rats. Grafts were perfused with and stored in low potassium dextran solution at 4°C for 6 hr. The recipients received 100% O2 or 98% O2 with 2% N 2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molecular analysis. Results. Gas exchange was markedly impaired in animals exposed to 100% O2, 2% N2, or 2% He. Hydrogen inhalation attenuated graft injury as indicated by significantly improved gas exchange 2 hr after reperfusion. Graft lipid peroxidation was significantly reduced in the presence of hydrogen, demonstrating antioxidant effects of hydrogen in the transplanted lungs. Lung cold I/R injury causes the rapid production and release of several proinflammatory mediators and epithelial apoptosis. Exposure to 2% H2 significantly blocked the production of several proinflammatory mediators and reduced apoptosis with induction of the antiapoptotic molecules B-cell lymphoma-2 and B-cell lymphoma-extra large. Conclusion. Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.

Original languageEnglish
Pages (from-to)1344-1351
Number of pages8
Issue number12
StatePublished - 27 Dec 2010
Externally publishedYes


  • Apoptosis
  • Experimental model
  • Hydrogen gas
  • Ischemia/reperfusion
  • Lung transplantation


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