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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

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.

Keywords

Hydrogen gas Donation after cardiac death Liver Rat Ischemia reperfusion 

Abbreviations

ATP

Adenosine triphosphate

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

CPA

Cardiopulmonary arrest

DCD

Donation after cardiac death

DBD

Donation after brain death

ECD

Expanded criteria donor

GSSG

Oxidized glutathione

GSH

Reduced glutathione

HPFs

High power fields

H2

Hydrogen gas

4-HNE

4-Hydroxy-2-nonenal

IRI

Ischemia and reperfusion injury

IPRL

Isolated perfused rat liver

JNK

c-jun N-terminal kinase

KHB

Krebs–Henseleit bicarbonate buffer

LDH

Lactate dehydrogenase

LPO

Lipid peroxidation

MDA

Malondialdehyde

MKK4

Mitogen-activated protein kinase 4

NADPH

Nicotinamide adenine dinucleotide phosphate

NMP

Normothermic machine perfusion

OCR

Oxygen consumption rate

PNF

Primary non-function

PVP

Portal vein pressure

PVR

Portal vein resistance

ROS

Reactive oxygen species

SCD

Standard criteria donor

SDS-PAGE

SDS polyacrylamide gel electrophoresis

TUNEL

Terminal deoxynucleotidyl transferase

Notes

Acknowledgements

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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