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.
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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
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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.
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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). https://doi.org/10.1007/s00595-018-1693-0
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DOI: https://doi.org/10.1007/s00595-018-1693-0