Oxygenated UW solution decreases ATP decay and improves survival after transplantation of DCD liver grafts

Background DCD liver grafts are known to be predisposed to primary nonfunction and ischemic cholangiopathy. Many DCD grafts are discarded because of older donor age or long warm ischemia times. Thus, it is critical to improve the quality of DCD liver grafts. Here, we have tested whether an enriched oxygen carrier added to the preservation solution can prolong graft survival and reduce biliary damage. Methods We assessed the ATP content decay of mouse liver grafts after cold ischemia, warm ischemia, and combined warm+cold ischemia. In addition, we used a rat model of liver transplantation to compare survival of DCD grafts preserved in high-oxygen solution (pre-oxygenated PFC+UW solution) vs. lower-oxygen solution (pre-oxygenated UW solution). Results ATP levels under UW preservation fall to less than 10% after 30 min of warm ischemia. Pre-oxygenated UW solution with PFC reached a significantly higher PaO2. After 45min of warm ischemia in oxygenated UW+PFC solution, grafts showed 63% higher levels of ATP (p=0.011). In addition, this was associated with better preservation of morphology when compared to grafts stored in standard UW solution. Animals that received DCD grafts preserved in higher oxygenation solution showed improved survival: 4 out of 6 animals survived long-term whereas all control group animals died within 24 hours. Conclusions The additional oxygen provided by PFC during static cold preservation of DCD livers can better sustain ATP levels, and thereby reduce the severity of ischemic tissue damage. PFC-based preservation solution extends the tolerance to warm ischemia, and may reduce the rate of ischemic cholangiopathy. Corresponding author: James F. Markmann MD, PhD, Transplant Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA, 02114, e-mail: jmarkmann@partners.org Authorship 1. Paulo N. Martins and James F. Markmann participated in research design, performance of the research and writing of the paper. 2. Timothy A. Berendsen, Heidi Yeh, Bote G. Bruinsma, Maria-Louisa Izamis, Sanna Op den Dries, Robert Porte, Martin L. Yarmush, and Korkut Uygun participated in performance of the research and writing of the paper. 3. Andrew R. Gillooly participated in writing of the paper. Disclosure The authors declare no conflicts of interest. Funding Departmental grant Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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