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

CONCLUSION

H 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.