Maintaining organ viability during preservation is an important factor for a successful outcome. The current status of liver transplantation across the world demands effective utilization of all available donor organs. It is clear that transplant surgeons are facing challenges with escalations in extended criteria donors, brain dead donors, as well as donation after circulatory death (DCD) organs. Development of methods for improving preservation and viability of organs becomes critical to consider such organs for transplantation. One component essential for tissue viability that is absent from current cold static preservation methods is tissue oxygenation. Despite decreased metabolism with cold static storage, energy consumption still occurs and a hypoxic state results in activation of cell disruptive anaerobic pathways.1,2
In this issue of Transplantation, Martins et al investigated the role of preoxygenated solutions in improving organ viability during static cold storage. The authors used perfluorocarbons as oxygen carrier, using a rat liver transplantation model they demonstrated that extended criteria organs can be preserved better with oxygen-rich preservation solution.3
Perfluorocarbons (PFC) are nonpolar fluorine saturated polycarbons capable of dissolving and carrying significantly greater concentration of oxygen than whole blood. Their size (average 0.15-0.2 μm micelle structures) allows penetration into the microvasculature where oxygen delivery by red blood cells may be compromised.4 Perfluorocarbon emulsions were investigated for organ preservation using animal models in the 1980s. They were successfully used in pancreas organ preservation using the well-described 2-layer method. The density of PFC results in preservation fluid being displaced to the top with the organ suspended in the PFC/preservation solution interphase.5,6 However, most of these isolated attempts were not followed through into clinical practice with other organs due to instability and adverse reactions associated with the first-generation PFC emulsions. The newer-generation PFC emulsion is more stable, and its role in organ preservation needs reevaluation.
Martins et al applied the 2-layer method to preserve DCD rat livers. This study was well designed, and the positive effects of oxygenated PFC solution were elegantly demonstrated using a rodent liver transplant survival model. One limitation is the authors' hypothesis that the rat livers received a continuous supply of oxygen using principles of gas dynamics, that is, oxygen diffusing passively from a high gradient (PFC solution) to a lower gradient (University of Wisconsin [UW] preservative solution). Although it may be possible that given the small volume of a rat liver, the entire liver, including bile ducts and blood vessels, could be exposed to oxygen-rich fluid in a static preservation environment, this concept would require further evaluation using a larger animal model and/or nontransplantable human livers. It is also possible that any portion of the liver touching the PFC layer could directly allow for oxygen to enter the liver parenchyma, and given the properties of PFC, this may be more efficient than oxygen transfer via static UW solution.
The authors of this commentary are personally evaluating of the role of PFC as oxygen carrier using a porcine DCD model. Our unpublished preliminary results indicate that a high tissue oxygen partial pressure (PtO2) can be achieved when the organ is flushed with oxygenated PFC + UW emulsion. However, the PtO2 declines slowly and returns to a baseline of 0 mm Hg within 60 minutes after a flush. This suggests to us that tissue oxygenation in human-sized organs could be better achieved in a dynamic setting.
There is a great interest in studying the role of machine perfusion in liver transplantation. The recent randomized trial from Europe demonstrated the safety and potential benefits of normothermic machine perfusion.7 However, the question of normothermic versus hypothermic perfusion for rehabilitation of extended criteria donor and DCD organs is still debated.7,8 Although there is a role for machine perfusion, these devices are cumbersome for transport to donor hospitals. There is still a potential role for a preoxygenated cold storage solution during transport because this would allow further assessments with machine perfusion at the transplant center.
The oxygen binding capacity of PFC is not dependent on temperature and as a result can function in any temperature setting. Additionally, PFC can ameliorate ischemic reperfusion injury as demonstrated in several animal studies.9,10
Transplant teams around the world are currently exploring several innovative strategies to minimize organ discard rates. Martins et al3 contributed important findings to the field of advanced organ preservation techniques.
PFC have unique properties that should be explored in well-designed studies. These biologically inert molecules may have significant role for better preservation of extended criteria liver organs both in a static and dynamic preservation setting.
1. Southard JH, Belzer FO. Organ preservation. Annu Rev Med
2. Clavien PA, Harvey PR, Strasberg SM. Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. Transplantation
3. Martins PN, Berendsen TA, Yeh H, et al. Oxygenated UW solution decreases ATP decay and improves survival after transplantation of DCD liver grafts. Transplantation
4. Hosgood SA, Nicholson ML. The role of perfluorocarbon in organ preservation. Transplantation
5. Kuroda Y, Kawamura T, Suzuki Y, et al. A new, simple method for cold storage of the pancreas using perfluorochemical. Transplantation
6. Noguchi H, Ueda M, Nakai Y, et al. Modified two-layer preservation method (M-Kyoto/PFC) improves islet yields in islet isolation. Am J Transplant
7. Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature
8. Schlegel A, Muller X, Dutkowski P. Hypothermic machine preservation of the liver: state of the art. Curr Transplant Rep
9. Ntinas A, Iliadis S, Alvanou Achparaki A, et al. The protective effect of oxygenated perfluorocarbons (PFCs) on intestinal ischemia reperfusion injury (I/R) in rabbits. Vasc Endovascular Surg
10. Forgiarini Junior LA, Holand AR, Forgiarini LF, et al. Endobronchial perfluorocarbon reduces inflammatory activity before and after lung transplantation in an animal experimental model. Mediators Inflamm