Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts

Ivan Linares-Cervantes, Juan Echeverri, Stuart Cleland, Johann Moritz Kaths, Roizar Rosales, Toru Goto, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Laura Mazilescu, Sujani Ganesh, Oyedele A. Adeyi, Paul Yip, Paulina Goryńska, Barbara Bojko, Krzysztof Goryński, David R. Grant, Nazia Selzner, Marcin Wąsowicz, Markus Selzner

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart-beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30′), 70 minutes (DCD70′), and 120 minutes (DCD120′) of warm ischemia were studied. The HBD, DCD30′, and DCD70′-groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120′-group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120′-group (>2 mmol/L) at 4 hours of perfusion (P =.04). The fold-urea increase was significantly lower in the DCD120′-group (≤0.4) compared to the other groups (≥0.65) (P =.01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120′-group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120′-group (≤1) (P <.01). Three hours after transplantation, the DCD120′-group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P =.02). Rocuronium levels were higher at all the time-points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.

Original languageEnglish (US)
Pages (from-to)2991-3005
Number of pages15
JournalAmerican Journal of Transplantation
Volume19
Issue number11
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Bibliographical note

Funding Information:
IL expresses his gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for its support for the Graduate program at University of Toronto. We thank Uwe Mummenhoff and the Birmingham family for their generous support. The study was supported by the Canadian National Transplant Research Program (CNTRP). This study received support from the 2016 ASTS‐Astellas Fellowship in Transplantation Grant.

Keywords

  • animal models: porcine
  • basic (laboratory) research/science
  • ischemia reperfusion injury (IRI)
  • liver allograft function/dysfunction
  • liver transplantation/hepatology
  • organ procurement and allocation
  • organ transplantation in general
  • primary nonfunction
  • translational research/science

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