Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model

Tomoyoshi Tamura, Motoaki Sano, Tadashi Matsuoka, Joe Yoshizawa, Ryo Yamamoto, Yoshinori Katsumata, Jin Endo, Koichiro Homma, Mayumi Kajimura, Masaru Suzuki, Eiji Kobayashi, Junichi Sasaki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Background:Hydrogen gas (H2) inhalation during hemorrhage stabilizes post-resuscitation hemodynamics, improving short-Term survival in a rat hemorrhagic shock and resuscitation (HS/R) model. However, the underlying molecular mechanism of H2in HS/R is unclear. Endothelial glycocalyx (EG) damage causes hemodynamic failure associated with HS/R. In this study, we tested the hypothesis that H2alleviates oxidative stress by suppressing xanthine oxidoreductase (XOR) and/or preventing tumor necrosis factor-Alfa (TNF-α)-mediated syndecan-1 shedding during EG damage.Methods:HS/R was induced in rats by reducing mean arterial pressure (MAP) to 35mm Hg for 60min followed by resuscitation. Rats inhaled oxygen or H2+ oxygen after achieving shock either in the presence or absence of an XOR inhibitor (XOR-I) for both the groups. In a second test, rats received oxygen alone or antitumor necrosis factor (TNF)-α monoclonal antibody with oxygen or H2. Two hours after resuscitation, XOR activity, purine metabolites, cytokines, syndecan-1 were measured and survival rates were assessed 6h after resuscitation.Results:H2and XOR-I both suppressed MAP reduction and improved survival rates. H2did not affect XOR activity and the therapeutic effects of XOR-I and H2were additive. H2suppressed plasma TNF-α and syndecan-1 expression; however, no additional H2therapeutic effect was observed in the presence of anti-TNF-α monoclonal antibody.Conclusions:H2inhalation after shock stabilized hemodynamics and improved survival rates in an HS/R model independent of XOR. The therapeutic action of H2was partially mediated by inhibition of TNF-α-dependent syndecan-1 shedding.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
Issue number3
Publication statusPublished - 2020 Sept 1


  • Fluid resuscitation
  • TNF-α
  • molecular hydrogen
  • syndecan-1
  • vascular permeability
  • xanthine oxidoreductase

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine


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