UW Supplementation with AP39 Improves Liver Viability Following Static Cold Storage.

Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H ₂ S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H ₂ S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H ₂ S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Korkut Uygun reports financial support was provided by Massachusetts General Hospital. Korkut Uygun reports a relationship with National Institutes of Health that includes: funding grants. Some authors declare competing interests. Drs. Uygun and Yeh have patent applications relevant to this study. Dr. Uygun, has a financial interest in and serves on the Scientific Advisory Board for Sylvatica Biotech Inc., a company focused on developing high subzero organ preservation technology. Competing interests for MGH investigators are managed by the MGH and MGB in accordance with their conflict-of-interest policies. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.