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Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts
Published on: August 13, 2014
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UW supplementation with AP39 improves liver viability following static cold storage
McLean Taggart1,2, Saige Holkup1, Alexandra Tchir1,2,3
1Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Scientific Reports
|January 9, 2025
Summary
Supplementing static cold storage with AP39, a hydrogen sulfide (H2S) donor, improves liver graft viability. AP39 reduces cellular damage and apoptosis, enhancing organ preservation for transplantation.
Area of Science:
- Organ transplantation
- Biochemistry
- Cellular metabolism
Background:
- Static cold storage of donor livers at 4°C inadequately preserves organs, leading to metabolic dysfunction, oxidative stress, and cell death.
- Hydrogen sulfide (H2S) offers protection against ischemia-reperfusion injury, but its rapid release is toxic.
- AP39, a novel mitochondrially targeted H2S donor, provides a safer, sustained release mechanism.
Purpose of the Study:
- To evaluate the efficacy of AP39 in preserving liver graft viability during 3-day static cold storage.
- To assess the impact of AP39 on liver function and cellular integrity post-preservation.
- To determine if AP39 mitigates damage during simulated transplantation.
Main Methods:
- Donor livers were stored for 3 days at 4°C, with or without AP39 supplementation.
- Following storage, livers were subjected to 6 hours of acellular normothermic machine perfusion.
- Key viability parameters, including resistance, cellular damage markers (ALT, AST), apoptosis, bile production, and energy charge, were measured.
Main Results:
- Livers stored with AP39 exhibited reduced perfusion resistance and lower levels of ALT and AST, indicating less cellular damage.
- AP39 treatment significantly decreased apoptosis in stored liver grafts.
- Bile production and energy charge were improved in AP39-supplemented livers compared to controls.
Conclusions:
- AP39 supplementation during static cold storage enhances liver graft viability.
- AP39 protects against cellular damage and apoptosis, improving organ quality for transplantation.
- This study demonstrates the potential of AP39 as a protective agent in organ preservation protocols.
