{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T17:02:19Z","timestamp":1759683739977,"version":"3.37.3"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"am","delay-in-days":372,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H04019","17H04271"],"award-info":[{"award-number":["15H04019","17H04271"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005683","name":"Kyoto University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005683","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia\/reperfusion injury (IRI). Molecular hydrogen (H<jats:sub>2<\/jats:sub>) 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\u2010ischemic H<jats:sub>2<\/jats:sub> 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\u2010hour CS in UW solution, livers were cold\u2010flushed with H<jats:sub>2<\/jats:sub> 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\u2010hour oxygenated reperfusion at 37\u00b0C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle\u2010treated controls (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS\u2010PV and \u2010PV + HA groups when compared with the others (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 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\u2010HA and \u2010PV + HA (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 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\u2010effectiveness, end\u2010ischemic HyFACS may be a novel pretransplant conditioning for cold\u2010stored donor organs.<\/jats:p>","DOI":"10.1002\/lt.25326","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T09:53:12Z","timestamp":1534585992000},"page":"1589-1602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hydrogen Flush After Cold Storage as a New End\u2010Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia\/Reperfusion Injury"],"prefix":"10.1097","volume":"24","author":[{"given":"Ichiro","family":"Tamaki","sequence":"first","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-6396","authenticated-orcid":false,"given":"Koichiro","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yermek","family":"Nigmet","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Hirao","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toyonari","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Inamoto","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiro","family":"Kusakabe","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuaki","family":"Tsuruyama","sequence":"additional","affiliation":[{"name":"Center for Anatomical, Pathological and Forensic Medical Research,Kyoto University Graduate School of Medicine,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene H.","family":"Tolba","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science and Experimental Surgery,Rheinisch\u2010Westf\u00e4lische Technische Hochschule Aachen University,Aachen,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Uemoto","sequence":"additional","affiliation":[{"name":"Department of Surgery,Division of Hepato\u2010Biliary\u2010Pancreatic Surgery and Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2018,11,8]]},"reference":[{"key":"lt25326-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1097\/SLA.0000000000001473","article-title":"First comparison of hypothermic oxygenated perfusion versus static cold storage of human donation after cardiac death liver transplants: an international\u2010matched case 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