冷保存後の水素フラッシュによる肝移植グラフトの虚血再灌流障害に対する体外処理法の開発
Cold storage (CS) is the standard method for organ preservation but is inherently linked to ischemia-reperfusion injury (IRI). This study developed a novel ex vivo conditioning technique called HyFACS, in which a hydrogen solution (1.0 ppm) is flushed through donor liver grafts at the end of the ischemic period via the portal vein (PV), hepatic artery (HA), or both. Using Wistar rat whole liver grafts subjected to 24-hour CS followed by 2-hour oxygenated reperfusion at 37°C, HyFACS significantly reduced portal venous pressure, transaminase levels, and HMGB1 release compared with controls. Hyaluronic acid clearance was improved by PV-route flushing, indicating sinusoidal endothelial preservation, while bile production and lactate dehydrogenase leakage were improved by HA-route flushing, reflecting biliary protection. Electron microscopy confirmed route-specific ultrastructural preservation. Mechanistically, oxidative damage was reduced and the glutathione/glutathione disulfide ratio in liver tissue was improved. These findings indicate that HyFACS confers route-dependent protection against hepatic IRI in cold-stored donor organs.
HyFACS reduces oxidative damage in liver tissue and restores the glutathione/glutathione disulfide ratio, thereby mitigating reperfusion-associated injury in cold-stored grafts. Route-specific delivery determines whether sinusoidal endothelia or biliary structures are preferentially protected.
Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).
See also:
https://h2-papers.org/en/papers/30120877