Francesca Maione1, Nicholas Gilbo2, Silvia Lazzaro2, Peter Friend3, Giovanni Camussi4, Renato Romagnoli1, Jacques Pirenne2, Ina Jochmans2, Diethard Monbaliu2. 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.
Abstract
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.
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.
Authors: Charles J Imber; Shawn D St Peter; Inigo Lopez de Cenarruzabeitia; Dave Pigott; Tim James; Richard Taylor; James McGuire; David Hughes; Andrew Butler; Michael Rees; Peter J Friend Journal: Transplantation Date: 2002-03-15 Impact factor: 4.939
Authors: C Grosse-Siestrup; S Nagel; V Unger; M Meissler; J Pfeffer; A Fischer; D A Groneberg Journal: J Pharmacol Toxicol Methods Date: 2001 Nov-Dec Impact factor: 1.950
Authors: E Schütz; E Wieland; A Hensel; P D Niedmann; A Dreiss; V W Armstrong; P Schuff-Werner; M Oellerich Journal: Clin Biochem Date: 1997-12 Impact factor: 3.281
Authors: Charles J Imber; Shawn D St Peter; Inigo Lopez de Cenarruzabeitia; Hugh Lemonde; Mike Rees; Andrew Butler; Peter T Clayton; Peter J Friend Journal: Am J Transplant Date: 2002-08 Impact factor: 8.086
Authors: Nicholas Gilbo; Tine Wylin; Veerle Heedfeld; Ina Jochmans; Jacques Pirenne; Peter Friend; Diethard Monbaliu Journal: Transplant Direct Date: 2021-12-13
Authors: Mohammed I Al-Sebayel; Yasser M El-Sheikh; Falah H Al-Mohanna; Saleh I Al Abbad; Yaser H Al Nemry; Ahmed Al-Jammali; Norah K Al-Zeer; Yazeed M Alsebayel; Hamad M Al-Bahli Journal: Saudi Med J Date: 2021-12 Impact factor: 1.422
Authors: Melanie Krüger; Alicia Ruppelt; Benjamin Kappler; Elke Van Soest; Roos Anne Samsom; Guy C M Grinwis; Niels Geijsen; J Bernd Helms; Marco Stijnen; Linda M Kock; Marco Rasponi; Hans S Kooistra; Bart Spee Journal: Bioengineering (Basel) Date: 2022-09-14