Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 510722
Title Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury
Author(s) Olthof, Pim B.; Golen, Rowan F. van; Meijer, Ben; Beek, Adriaan A. van; Bennink, Roelof J.; Verheij, Joanne; Gulik, Thomas M. van; Heger, Michal
Source Biochimica et Biophysica Acta. Molecular Basis of Disease 1863 (2017)2. - ISSN 0925-4439 - p. 375 - 385.
DOI http://dx.doi.org/10.1016/j.bbadis.2016.10.022
Department(s) Cell Biology and Immunology
Publication type Refereed Article in a scientific journal
Publication year 2017
Abstract

Background Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate immune parameters as endpoints. Methods Mice (C57Bl/6J) were subjected to sham surgery, 30 min, or 60 min of partial hepatic ischemia. Liver function was measured after 24 h using intravital microscopy and spectroscopy. Innate immune activity was assessed at 6 and 24 h of reperfusion using mRNA and cytokine arrays. Liver inflammation and function were profiled in two patient cohorts subjected to I/R during liver resection to validate the preclinical results. Results In mice, plasma ALT levels and the degree of hepatic necrosis were strongly correlated. Liver function was bound by a narrow damage threshold and was severely impaired following 60 min of ischemia. Severe ischemia (60 min) evoked a neutrophil-dominant immune response, whereas mild ischemia (30 min) triggered a monocyte-driven response. Clinical liver I/R did not compromise liver function and displayed a cytokine profile similar to the mild I/R injury model. Conclusions Mouse models using ≤ 30 min of ischemia best reflect the clinical liver I/R injury profile in terms of liver function dynamics and type of immune response. General significance This short duration of ischemia therefore has most translational value and should be used to increase the prospects of developing effective interventions for hepatic I/R.

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