Use of a Third-Generation Perfluorocarbon for Preservation of Rat DCD Liver Grafts

Bezinover, Dmitri; Ramamoorthy, Saravanan; Uemura, Todahiro; Kadry, Zakiyah; McQuillan, Patrick; Mets, Berend; Falcucci, Octavio; Rannels, Sharon; Ruiz‐Velasco, Victor; Spiess, Bruce D.; Liang, Jane; Mani, Haresh; Lou, Xi; Janicki, Piotr K.

doi:10.1016/j.jss.2011.02.046

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…The results of the present study demonstrated that the oxygenation of DCD liver grafts provided by PFC attenuated liver IRI and improved the survival rate after DCD LT in the rat model. Although previous investigations found that PFCs can be beneficial with ex vivo reperfusion models, there have been no studies to date that investigated the effect of PFC using an in vivo DCD LT model. To the best of our knowledge, this would be the first study to investigate the impact of PFC on outcomes after DCD LT.…”

Section: Discussionmentioning

confidence: 99%

“…However, other previous experimental attempts in the liver and lung were not very convincing, possibly because of the structure, thickness, and density of these organs . The technical innovation of PFC emulsion allowed us to use this “hydrophobic” compound intravenously, and the recent generation of PFC emulsions has been proven useful in DCD liver graft preservation in ex vivo experimental models . The necessity of DCD liver graft oxygenation during cold preservation has also been recently revealed in hypothermic machine perfusion models .…”

Section: Discussionmentioning

confidence: 99%

“…PFCs have been used in studies of organ preservation . The study of the PFC for DCD liver grafts was performed by Bezinover et al with the rat liver preservation model . The study demonstrated that the addition of PFC to the University of Wisconsin (UW) solution significantly decreased the histologic damage in rat DCD liver grafts during cold preservation.…”

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confidence: 99%

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Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats

et al. 2017

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The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats

et al. 2017

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“…Most groups recognize the need for a specialist oxygen carrier, although dissolving enough oxygen in a simple solution is theoretically possible using hyperbaric conditions . Specialist oxygen carriers that have been considered include perfluorocarbon molecules, but increasingly the consensus is to use erythrocytes. Blood‐based perfusates have been the basis of the majority of recent publications in this area .…”

Section: Implementations Of Normothermic Perfusion Of the Livermentioning

confidence: 99%

Normothermic liver preservation: a new paradigm?

2015

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Summary Despite increasing donor numbers, waiting lists and pre‐transplant mortality continue to grow in many countries. The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia‐reperfusion injury (IRI). Transplantation of marginal donor organs has led to renewed interest in new techniques which have the potential to improve the quality of preservation, assess the quality of the organ and allow repair of the donor organ prior to transplantation. If successful, such techniques would not only improve the outcome of currently transplanted marginal livers, but also increase the donor pool. Experimental evidence suggests that preservation under near physiological conditions of temperature and oxygenation abrogates IRI. Normothermic perfusion maintains the organ in a physiological state, avoiding the depletion of cellular energy and the accumulation of waste products, which occurs with static cold storage. It enables viability assessment prior to transplantation thereby reducing the risk of transplanting inherently marginal organs. Here we review the use of normothermic machine perfusion as a means of organ preservation.

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“…Perfluorocarbon (PFC) liquids have been investigated as a medical application for many years. These synthetic liquids are essentially bioinert and have no known deleterious histological, cellular, or biochemical effects [26,27,28,29,30]. The two-layer method (TLM) uses an oxygenated PFC and UW solution to preserve pancreases for whole organ and islet transplantation; TLM enhances pancreatic functions and increases islet cell yield after cold preservation compared with simple UW cold storage [25].…”

Section: Introductionmentioning

confidence: 99%

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

Murakami²,

Aoki³

et al. 2015

Eur Surg Res

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Background: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. Materials and Methods: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. Results: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. Conclusion: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

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Use of a Third-Generation Perfluorocarbon for Preservation of Rat DCD Liver Grafts

Cited by 19 publications

References 28 publications

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats

Normothermic liver preservation: a new paradigm?

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

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