Lung Transplant-Induced Ischemia Reperfusion Injury in Rats..pdf

BASIC AND EXPERIMENTAL RESEARCH Inhaled Hydrogen Gas Therapy for Prevention of Lung Transplant-Induced Ischemia/Reperfusion Injury in Rats Tomohiro Kawamura,1,2,3 Chien-Sheng Huang,1,4 Naobumi Tochigi,5 Sungsoo Lee,1 Norihisa Shigemura,1 Timothy R. Billiar,6 Meinoshin Okumura,2 Atsunori Nakao,1,3,5,7 and Yoshiya Toyoda1,3 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 anti- apoptotic 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% N2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molec- ular 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 exten