Pharmacokinetics of a single inhalation of hydrogen gas in pigs.

The benefits of inhaling hydrogen gas (H2) have been widely reported but its pharmacokinetics have not yet been sufficiently analyzed. We developed a new experimental system in pigs to closely evaluate the process by which H2 is absorbed in the lungs, enters the bloodstream, and is distributed, metabolized, and excreted. We inserted and secured catheters into the carotid artery (CA), portal vein (PV), and supra-hepatic inferior vena cava (IVC) to allow repeated blood sampling and performed bilateral thoracotomy to collapse the lungs. Then, using a hydrogen-absorbing alloy canister, we filled the lungs to the maximum inspiratory level with 100% H2. The pig was maintained for 30 seconds without resuming breathing, as if they were holding their breath. We collected blood from the three intravascular catheters after 0, 3, 10, 30, and 60 minutes and measured H2 concentration by gas chromatography. H2 concentration in the CA peaked immediately after breath holding; 3 min later, it dropped to 1/40 of the peak value. Peak H2 concentrations in the PV and IVC were 40% and 14% of that in the CA, respectively. However, H2 concentration decay in the PV and IVC (half-life: 310 s and 350 s, respectively) was slower than in the CA (half-life: 92 s). At 10 min, H2 concentration was significantly higher in venous blood than in arterial blood. At 60 min, H2 was detected in the portal blood at a concentration of 6.9-53 nL/mL higher than at steady state, and in the SVC 14-29 nL/mL higher than at steady state. In contrast, H2 concentration in the CA decreased to steady state levels. This is the first report showing that inhaled H2 is transported to the whole body by advection diffusion and metabolized dynamically.

Déclaration de conflit d'intérêts

The authors would like to declare the following patents/patent applications associated with this research: S.O. is a founder and CEO of Mitos, Co., Ltd, and the holder of a patent for the use of H2. M.S. and E.K. receive advisory fees from Doctors Man Co., Ltd. M.S. receives advisory fees and research fees from Taiyo Nippon Sanso. Author M.S. is the registered inventor of the following patent jointly filed by Keio University and Taiyo Nippon Sanso. Hydrogen mixed gas supply device for medical purposes (Patent number: 5631524), Medicinal composition for improving prognosis after restart of patient's own heartbeat (Application number PCT/JP2016/088172), Medicinal composition for improving and/or stabilizing circulatory dynamics after onset of hemorrhagic shock (Application number PCT/JP2017/026431). In addition to these, there are three other patents in which the name of the invention is only in Japanese and is not described in English. Here is the name of the invention, which is a literal translation of Japanese into English. Pharmaceutical compositions for reducing weight loss after organ harvesting (Joint application with Keio University and Taiyo Nippon Sanso) Method for generating organ preservation solution containing hydrogen and organ preservation solution containing hydrogen (Joint application with Keio University and Doctors Man; Application number PCT/JP2019/045790). Information about Joint Application between Keio University and Taiyo Nippon Sanso has been uploaded as an attachment. This does not alter our adherence to PLOS ONE policies on sharing data and materials.