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

Abstract

This study investigated the molecular mechanisms underlying the hemodynamic benefits of hydrogen gas (H2) inhalation in a rat hemorrhagic shock and resuscitation (HS/R) model. Shock was induced by lowering mean arterial pressure to 35 mmHg for 60 minutes, followed by resuscitation. H2 inhalation and xanthine oxidoreductase inhibition (XOR-I) each independently stabilized blood pressure and improved 6-hour survival rates, with additive effects observed when combined. Notably, H2 did not alter XOR enzymatic activity, indicating an XOR-independent mechanism. Plasma TNF-α and syndecan-1 levels were both reduced by H2 inhalation. When anti-TNF-α monoclonal antibody was co-administered, no further benefit from H2 was detected, suggesting that H2 acts primarily by suppressing TNF-α-mediated shedding of syndecan-1 from the endothelial glycocalyx, thereby preserving vascular integrity and hemodynamic function after resuscitation.

Mechanism

H2 inhalation suppresses TNF-α production, thereby inhibiting syndecan-1 shedding from the endothelial glycocalyx. This preserves vascular barrier function and stabilizes hemodynamics after hemorrhagic shock, operating independently of xanthine oxidoreductase activity.