UW Supplementation with AP39 Improves Liver Viability Following Static Cold Storage

Area of Science:

• Organ preservation
• Transplantation immunology
• Biomedical engineering

Background:

• Static cold storage of donor livers at 4°C inadequately halts metabolism, causing ATP depletion, oxidative stress, and cell death.
• Hydrogen sulfide (H2S) protects against ischemia-reperfusion injury, but its rapid release is toxic.
• AP39, a mitochondrially targeted H2S donor, offers controlled release and has shown protective effects in other organs.

Purpose of the Study:

• To investigate the efficacy of AP39 supplementation during 3-day static cold storage for improving liver graft viability.
• To assess the impact of AP39 on liver function and cellular integrity post-preservation.

Main Methods:

• Donor livers were stored for 3 days at 4°C, with some supplemented with AP39.
• Following storage, livers underwent 6 hours of acellular normothermic machine perfusion as a transplantation model.
• Key viability parameters including resistance, cellular damage markers (ALT, AST), apoptosis, bile production, glucose levels, and energy charge were measured.

Main Results:

• Livers stored with AP39 exhibited reduced perfusion resistance and lower levels of cellular damage markers (ALT and AST).
• AP39 supplementation significantly decreased apoptosis.
• Improved bile production, glucose metabolism, and energy charge were observed in AP39-treated livers.

Conclusions:

• AP39 supplementation during static cold storage enhances liver graft viability.
• AP39 mitigates cellular damage and apoptosis, improving functional parameters after preservation.
• This approach holds promise for improving outcomes in liver transplantation.