Takahisa Ishikawa1, Shingo Shimada1, Moto Fukai2, Taichi Kimura3, Kouhei Umemoto1, Kengo Shibata1, Masato Fujiyoshi1, Sunao Fujiyoshi1, Takahiro Hayasaka1, Norio Kawamura4, Nozomi Kobayashi1, Tsuyoshi Shimamura5, Akinobu Taketomi1. 1. Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-Ku, Sapporo, 060-8638, Japan. 2. Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-Ku, Sapporo, 060-8638, Japan. db7m-fki@hotmail.co.jp. 3. Laboratory of Cancer Research, Department of Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 4. Department of Transplant Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 5. Division of Organ Transplantation, Central Clinical Facilities, Hokkaido University Hospital, Sapporo, Japan.
Abstract
BACKGROUND AND PURPOSE: We reported previously that hydrogen gas (H2) reduced hepatic ischemia and reperfusion injury (IRI) after prolonged cold storage (CS) of livers retrieved from heart-beating donors. The present study was designed to assess whether H2 reduced hepatic IRI during donation of a cardiac death (DCD) graft with subsequent CS. METHODS: Rat livers were harvested after 30-min cardiac arrest and stored for 4 h in University of Wisconsin solution. The graft was reperfused with oxygenated buffer, with or without H2 (H2 or NT groups, respectively), at 37° for 90 min on isolated perfused rat liver apparatus. RESULTS: In the NT group, liver enzyme leakage, apoptosis, necrosis, energy depletion, redox status, impaired microcirculation, and bile production were indicative of severe IRI, whereas in the H2 group these impairments were significantly suppressed. The phosphorylation of cytoplasmic MKK4 and JNK were enhanced in the NT group and suppressed in the H2 group. NFkB-p65 and c-Fos in the nucleus were unexpectedly unchanged by IRI regardless of H2 treatment, indicating the absence of inflammation in this model. CONCLUSION: H2 was observed to ameliorate IRI in the DCD liver by maintaining microcirculation, mitochondrial functions, and redox status, as well as suppressing the cytoplasmic MKK4-JNK-mediated cellular death pathway.
BACKGROUND AND PURPOSE: We reported previously that hydrogen gas (H2) reduced hepatic ischemia and reperfusion injury (IRI) after prolonged cold storage (CS) of livers retrieved from heart-beating donors. The present study was designed to assess whether H2 reduced hepatic IRI during donation of a cardiac death (DCD) graft with subsequent CS. METHODS:Rat livers were harvested after 30-min cardiac arrest and stored for 4 h in University of Wisconsin solution. The graft was reperfused with oxygenated buffer, with or without H2 (H2 or NT groups, respectively), at 37° for 90 min on isolated perfused rat liver apparatus. RESULTS: In the NT group, liver enzyme leakage, apoptosis, necrosis, energy depletion, redox status, impaired microcirculation, and bile production were indicative of severe IRI, whereas in the H2 group these impairments were significantly suppressed. The phosphorylation of cytoplasmic MKK4 and JNK were enhanced in the NT group and suppressed in the H2 group. NFkB-p65 and c-Fos in the nucleus were unexpectedly unchanged by IRI regardless of H2 treatment, indicating the absence of inflammation in this model. CONCLUSION:H2 was observed to ameliorate IRI in the DCD liver by maintaining microcirculation, mitochondrial functions, and redox status, as well as suppressing the cytoplasmic MKK4-JNK-mediated cellular death pathway.
Entities:
Keywords:
Donation after cardiac death; Hydrogen gas; Ischemia reperfusion; Liver; Rat
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