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.
KeywordsHydrogen gas Donation after cardiac death Liver Rat Ischemia reperfusion
Donation after cardiac death
Donation after brain death
Expanded criteria donor
High power fields
Ischemia and reperfusion injury
Isolated perfused rat liver
c-jun N-terminal kinase
Krebs–Henseleit bicarbonate buffer
Mitogen-activated protein kinase 4
Nicotinamide adenine dinucleotide phosphate
Normothermic machine perfusion
Oxygen consumption rate
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.
- 36.Zheng Y, Zhu D. Molecular hydrogen therapy ameliorates organ damage induced by sepsis. Oxidative Med Cell Longev. 2016;2016:5806057.Google Scholar