Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion

Area of Science:

• Hepatology
• Transplantation immunology
• Mitochondrial biology

Background:

• Cold ischemia-reperfusion (IR) injury is a primary cause of liver allograft dysfunction.
• Mitochondria are key targets of IR injury.
• Methane (CH4) exhibits protective effects in hypoxic and IR conditions, influencing mitochondrial biology.

Purpose of the Study:

• To investigate the potential of methane (CH4)-enriched preservation solution for protecting liver allografts against cold IR injury.
• To evaluate the impact of CH4 on mitochondrial function and graft viability in a preclinical liver transplantation model.

Main Methods:

• Liver grafts were preserved for 24 hours in standard histidine-tryptophan-ketoglutarate (HTK) or CH4-enriched HTK (HTK-CH4) solution.
• Graft viability was assessed during 60 minutes of normothermic isolated reperfusion.
• Mitochondrial oxidative phosphorylation capacity and extramitochondrial Ca2+ flux were measured using high-resolution respirometry.

Main Results:

• CH4-preserved grafts exhibited increased oxygen and glucose consumption and decreased hepatocellular damage.
• Mitochondrial oxidative phosphorylation capacity was significantly better preserved in the HTK-CH4 group.
• A higher extramitochondrial Ca2+ flux was observed in grafts stored with HTK-CH4.

Conclusions:

• Methane (CH4) directly impacts hepatic mitochondrial function and extramitochondrial Ca2+ fluxes.
• CH4-enriched preservation solution enhances liver graft defense against cold IR injury.
• This approach shows promise for improving organ viability and post-transplant outcomes.