Hydrogen Flush Protects Donor Livers from Transplant Damage
- Authors
- Ichiro Tamaki, Koichiro Hata, Yusuke Okamura, Yermek Nigmet, Hirofumi Hirao, Toyonari Kubota, Osamu Inamoto, Jiro Kusakabe, Toru Goto, Tetsuya Tajima, Junichi Yoshikawa, Hirokazu Tanaka, Tatsuaki Tsuruyama, Rene H. Tolba, Shinji Uemoto
- Journal
- Liver Transplantation
- Year
- 2018
- DOI
- 10.1002/lt.25326
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Ischemia/Reperfusion Injury
- Body System
- Hepatic
TL;DR
A new method called hydrogen flush after cold storage (HyFACS) significantly reduces damage to liver organs preserved for transplant by flushing them with a hydrogen solution.
Key Finding
Hydrogen flush after cold storage significantly reduced liver damage markers and preserved organ function in rat livers, with benefits varying depending on whether the hydrogen solution was delivered through the portal vein, hepatic artery, or both.
Summary
Researchers tested a new method called hydrogen flush after cold storage (HyFACS) to protect liver organs from damage during transplantation. They stored rat livers in cold solution for 24 hours, then flushed them with hydrogen-enriched solution before transplant. Compared to untreated livers, the hydrogen-treated livers showed less damage, better function, and reduced signs of cellular injury caused by oxygen deprivation and restoration.
Practical Takeaway
This is early-stage research conducted only in rats, so it cannot yet inform human health decisions. The findings suggest hydrogen may help protect donor organs during transplantation, but human clinical trials would be needed to determine if this approach is safe and effective for transplant patients.
Abstract
Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end‐ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24‐hour CS in UW solution, livers were cold‐flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2‐hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle‐treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS‐PV and ‐PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS‐HA and ‐PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost‐effectiveness, end‐ischemic HyFACS may be a novel pretransplant conditioning for cold‐stored donor organs.