Surgery Today

, Volume 48, Issue 12, pp 1081–1088 | Cite as

Post-reperfusion hydrogen gas treatment ameliorates ischemia reperfusion injury in rat livers from donors after cardiac death: a preliminary study

  • Takahisa Ishikawa
  • Shingo Shimada
  • Moto FukaiEmail author
  • Taichi Kimura
  • Kouhei Umemoto
  • Kengo Shibata
  • Masato Fujiyoshi
  • Sunao Fujiyoshi
  • Takahiro Hayasaka
  • Norio Kawamura
  • Nozomi Kobayashi
  • Tsuyoshi Shimamura
  • Akinobu Taketomi
Original Article


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.


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.


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.


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.


Hydrogen gas Donation after cardiac death Liver Rat Ischemia reperfusion 



Adenosine triphosphate


Alanine aminotransferase


Aspartate aminotransferase


Cardiopulmonary arrest


Donation after cardiac death


Donation after brain death


Expanded criteria donor


Oxidized glutathione


Reduced glutathione


High power fields


Hydrogen gas




Ischemia and reperfusion injury


Isolated perfused rat liver


c-jun N-terminal kinase


Krebs–Henseleit bicarbonate buffer


Lactate dehydrogenase


Lipid peroxidation




Mitogen-activated protein kinase 4


Nicotinamide adenine dinucleotide phosphate


Normothermic machine perfusion


Oxygen consumption rate


Primary non-function


Portal vein pressure


Portal vein resistance


Reactive oxygen species


Standard criteria donor


SDS polyacrylamide gel electrophoresis


Terminal deoxynucleotidyl transferase



We thank Mr. Masatoshi Horigome for the animal care, Ms. Sayaka Miyoshi for technical assistance, and the staff of the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, for their kind cooperation.

Compliance with ethical standards

Conflict of interest

We have no conflicts of interest to declare.


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Takahisa Ishikawa
    • 1
  • Shingo Shimada
    • 1
  • Moto Fukai
    • 1
    Email author
  • Taichi Kimura
    • 2
  • Kouhei Umemoto
    • 1
  • Kengo Shibata
    • 1
  • Masato Fujiyoshi
    • 1
  • Sunao Fujiyoshi
    • 1
  • Takahiro Hayasaka
    • 1
  • Norio Kawamura
    • 3
  • Nozomi Kobayashi
    • 1
  • Tsuyoshi Shimamura
    • 4
  • Akinobu Taketomi
    • 1
  1. 1.Department of Gastroenterological Surgery I, Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Laboratory of Cancer Research, Department of Pathology, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Department of Transplant Surgery, Graduate School of MedicineHokkaido UniversitySapporoJapan
  4. 4.Division of Organ Transplantation, Central Clinical FacilitiesHokkaido University HospitalSapporoJapan

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