Protective Effect of Hydrogen Gas Inhalation on Muscular Damage using a Mouse Hind Limb Ischemia Reperfusion Injury Model.

Background: Ischemia reperfusion (IR) injury is one of the leading causes of tissue damage and dysfunction, in particular free tissue transfer, traumatically amputated extremity, and prolonged tourniquet application during extremity surgery. Here, we investigated therapeutic effects of hydrogen (H2) gas on skeletal muscle IR injury. Methods: We compared the concentration of H2 in a muscle on intraperitoneal administration of HRS H2-rich saline and on inhalation of H2 gas. Animals were subjected to IR. Mice were treated with inhalation of H2 gas, and the hind gastrocnemius muscle was collected. Muscle morphology and inflammatory change was evaluated after IR. Moreover, a footprint test was performed to assess the functional effect of H2. Results: H2 concentration of tissue was significantly higher, and the elevated level was maintained longer by H2 gas inhalation than by intraperitoneal administration of HRS. Infarct zone and area with loss of tissue structure and marked cellular infiltration were significantly decreased in groups treated by H2 gas inhalation during IR; however, these effects were not observed by post-treatment of H2. One week after IR, mice that had been pre-treated with H2 gas were recovered faster and achieved smoother walking in appearance compared to mice of the other groups as assessed by the footprint test. Conclusion: Inhalation of H2 gas attenuates muscle damage, inhibits inflammatory response, and enhances functional recovery. These findings suggest that the optimal route for H2 delivery is continuous inhalation of H2 gas, which could be a novel clinical mode of treatment in IR injury. (C)2017American Society of Plastic Surgeons

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