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Updated: Aug 9, 2025
Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts
Published on: August 13, 2014
Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion
Tamara Horváth1, Lilla Sándor1, Bálint Baráth1,2
1Institute of Surgical Research, University of Szeged, H-6724 Szeged, Hungary.
Abstract:
Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine-tryptophan-ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR.
Insights
Methane (CH4) enriched preservation solution improved liver graft function by protecting mitochondria during cold storage. This method enhanced organ viability and reduced damage after transplantation in a rat model.
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.
