Molecular hydrogen as a potential treatment of chronic rejection after experimental lung transplantation

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Lung transplantation (LTx) has become an effective clinical treatment for patients with end-stage pulmonary diseases. However, in spite of improved surgical techniques, donor organ preservation solutions and immunosuppression regimes, chronic allograft rejection (CR), is a severe complication in the form of obliterative bronchiolitis (BO) and vasculopathy and limits longterm allograft survival. Multiple factors seem to be responsible for the development of CR. Besides acute rejections (AR) and lymphocytic bronchiolitis, oxidative stress plays a central role in the development of CR. However, suitable therapeutic options are still lacking. Many animal experiments with molecular hydrogen (H2) therapy were already carried out in a variety of disease fields. However, studies about the treatment of CR after LTx with H2 are still missing. Scavenging of free radicals by molecular hydrogen may act preventively or therapeutically. The aim of this study is to investigate the efficency of H2 as a therapeutical option of CR after experimental LTx.In a one-sided, orthotopic lung transplant model in rats (F344 in WKY) four study groups are designed to investigate the treatment of CR by means of H2. In this animal model, H2 should be used inhalatively (2% in a room air chamber) in addition to H2-enriched drinking water as well as via an intraperitoneal injection with H2-enriched physiological saline solution.The first group is based on the effect of H2 on CR alone. In two other groups, based on the current clinical situation to treat the CR after LTx, immunosuppressants (mycophenolate mofetil and everolimus) are used as a combination therapy with H2. Since it is known that the combination of various receptor tyrosine kinase inhibitors (RTK-I) reduced CR in animal experiments, the final study group is a combination of RTK Is with molecular H2. In addition to the question of the treatment of the CR by means of H2 after experimental LTx, this study will continue to contribute to the clarification of the pathological mechanism of the CR after LTx.