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


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.

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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

H2 :

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


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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.

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Correspondence to Moto Fukai.

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Ishikawa, T., Shimada, S., Fukai, M. et al. Post-reperfusion hydrogen gas treatment ameliorates ischemia reperfusion injury in rat livers from donors after cardiac death: a preliminary study. Surg Today 48, 1081–1088 (2018).

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  • Hydrogen gas
  • Donation after cardiac death
  • Liver
  • Rat
  • Ischemia reperfusion