Paulo N Martins1,2, Timothy A Berendsen3, Heidi Yeh2, Bote G Bruinsma4, Maria-Louisa Izamis4, Sanna Op den Dries3, Andrew R Gillooly1, Robert Porte3, Martin L Yarmush4,5, Korkut Uygun1, James F Markmann2. 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.
Abstract
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.
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.
Authors: Pierre Alix; David Val-Laillet; Bruno Turlin; Ismail Ben Mosbah; Agnes Burel; Eric Bobillier; Claude Bendavid; Eric Delpy; Franck Zal; Anne Corlu; Karim Boudjema Journal: JHEP Rep Date: 2020-05-08
Authors: Isabel M A Brüggenwirth; Willemijn S van der Plas; Otto B van Leeuwen; Adam M Thorne; Michel Rayar; Vincent E de Meijer; Robert J Porte Journal: Artif Organs Date: 2021-12-16 Impact factor: 2.663