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 (H ₂ ) 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 H ₂ 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 H ₂ (H ₂ 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 H ₂ group these impairments were significantly suppressed. The phosphorylation of cytoplasmic MKK4 and JNK were enhanced in the NT group and suppressed in the H ₂ group. NFkB-p65 and c-Fos in the nucleus were unexpectedly unchanged by IRI regardless of H ₂ treatment, indicating the absence of inflammation in this model.
Conclusion: H ₂ 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.