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Porcine Isolated Liver Perfusion for the Study of Ischemia Reperfusion Injury: A Systematic Review

Maione, Francesca, MD1; Gilbo, Nicholas, MD2; Lazzaro, Silvia, MD2; Friend, Peter, PhD3; Camussi, Giovanni, MD4; Romagnoli, Renato, MD1; Pirenne, Jacques, PhD2; Jochmans, Ina, PhD2; Monbaliu, Diethard, PhD2

doi: 10.1097/TP.0000000000002156
Reviews

Background Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated.

Methods We systematically reviewed the current experimental setups for ILP and parameters of interest reflecting IRI.

Results Isolated liver perfusion was never compared with transplantation in animals. Considerable variability exists between setups, and comparative data are unavailable. Experience so far suggests that centrifugal pump(s) with continuous flow are preferred to reduce the risk of embolism. Hepatic outflow can be established by cannulation of the inferior vena cava or freely drained in an open bath. Whole blood at approximately 38°C, hematocrit of 20% or greater, and the presence of leukocytes to trigger inflammation is considered the optimal perfusate. A number of parameters related to the 4 liver compartments (hepatocyte, cholangiocyte, endothelium, immune cells) are available; however, their significance and relation to clinical outcomes is not well described.

Conclusions Porcine ILP provides a reproducible model to study early IRI events. As all models, it has its limitations. A standardization of the setup would allow comparison of data and progress in the field.

The authors summarize the methods of isolated liver perfusion (ILP) together with the parameters for evaluation of ischemia reperfusion injury. ILP is also evaluated as a model to replace liver transplantation in animals with the benefits and limitations.

1 Liver Transplantation Center and General Surgery 2U, AOU Città della Salute e della Scienza di Torino, University of Torino, Italy.

2 Abdominal Transplant Surgery, Department of Microbiology and Immunology, KU Leuven, University Hospitals, Leuven, Belgium.

3 Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.

4 Molecular Biotechnology Center, Department of Medical Sciences, University of Turin, Italy.

Received 20 October 2017. Revision received 24 January 2018.

Accepted 3 February 2018.

F.M. and N.G. contributed equally.

J.P. holds a named chair at the KU Leuven from the Institut Georges Lopez. J.P., D.M., and I.J. hold a named chair at the KU Leuven from the “Centrale Afdeling voor Fractionering.” D.M. is a senior clinical investigator of the research foundation Flanders, Belgium (FWO 18B1916N). No specific funding was sought for the present study.

The authors declare no conflicts of interest.

F.M., N.G., I.J. and D.M. designed the study, acquired, analyzed and interpreted the data, wrote the manuscript and take responsibility for the integrity of the data and the accuracy of the data analysis. S.L. acquired, analyzed and interpreted the data. G.C., R.R., J.P., and P.F. contributed to the interpretation of data, critically revised and approved the manuscript and take responsibility for the integrity of the data and the accuracy of the data analysis.

Correspondence: Diethard Monbaliu, MD, PhD, Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. (diethard.monbaliu@uzleuven.be).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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