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

AbstractBackgroundUnderstanding 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.MethodsWe systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI.ResultsILP was never compared to transplantation in animals. Considerable variability exists between set-ups 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 ~38°C, hematocrit ≥ 20%, 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.ConclusionsPorcine ILP provides a reproducible model to study early IRI events. As all models it has its limitations. A standardization of the set-up would allow comparison of data and progress in the field. 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 set-ups for ILP and parameters of interest reflecting IRI. Results ILP was never compared to transplantation in animals. Considerable variability exists between set-ups 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 ~38°C, hematocrit ≥ 20%, 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 set-up would allow comparison of data and progress in the field. These authors contributed equally, Francesca Maione, MD, Nicholas Gilbo. Correspondence: Diethard Monbaliu, MD, PhD, Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, B-3000 Leuven (Belgium), E-mail: diethard.monbaliu@uzleuven.be Authorship: FM, NG, IJ and DM 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. SL acquired, analyzed and interpreted the data. GC, RR, JP and PF 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. Disclosure: The authors declare no conflicts of interest with regard to the conduction and reporting of the results of the systematic review presented in this manuscript, in line with the editorial policy of Transplantation Funding: JP holds a named chair at the KU Leuven from the Institut Georges Lopez. JP, DM, and IJ hold a named chair at the KU Leuven from the "Centrale Afdeling voor Fractionering". DM is a senior clinical investigator of the research foundation Flanders, Belgium (FWO 18B1916N). No specific funding was sought for the present study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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