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Oxygenated UW Solution Decreases ATP Decay and Improves Survival After Transplantation of DCD Liver Grafts

Martins, Paulo N., MD, PhD1,2; Berendsen, Timothy A., MSc, MD3; Yeh, Heidi, MD2; Bruinsma, Bote G., MD, PhD4; Izamis, Maria-Louisa, PhD4; Op den Dries, Sanna, MD, PhD3; Gillooly, Andrew R.1; Porte, Robert, MD, PhD3; Yarmush, Martin L., MD, PhD4,5; Uygun, Korkut, PhD1; Markmann, James F., MD, PhD2

doi: 10.1097/TP.0000000000002530
Original Basic Science—Liver

Background Donation after circulatory death (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 adenosine triphosphate (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 (preoxygenated perfluorocarbon [PFC] + University of Wisconsin [UW] solution) versus lower oxygen solution (preoxygenated UW solution).

Results Adenosine triphosphate levels under UW preservation fall to less than 10% after 30 minutes of warm ischemia. Preoxygenated UW solution with PFC reached a significantly higher PaO2. After 45 minutes 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.

The authors explore the protective effect of additional oxygen provided by Perfluorocarbons during static cold preservation of donation after cardiac death livers in a rat model. It is demonstrated that Oxygenated University of Wisconsin solution may attenuate ischemia reperfusion injury and improve graft survival.

1 Transplant Division, Department of Surgery, University of Massachusetts, Worcester, MA.

2 Transplant Center, Massachusetts General Hospital, Harvard University, Boston, MA.

3 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

4 Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Boston, MA.

5 Department of Biomedical Engineering, Rutgers University, Piscataway, NJ.

Received 13 August 2018. Revision received 27 September 2018.

Accepted 9 October 2018.

The authors declare no conflicts of interest.

Funding: Departmental grant.

P.N.M. and J.F.M. participated in research design, performance of the research, and writing of the article. T.A.B., H.Y., B.G.B., M.-L.I., S.O.d.D., R.P., M.L.Y., and K.U. participated in performance of the research and writing of the article. A.R.G. participated in writing of the article.

Correspondence: James F. Markmann, MD, PhD, Transplant Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. (jmarkmann@partners.org).

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