Intermittent ischemia enhances the uptake of indocyanine green to livers subject to ischemia and reperfusion

Authors

  • Mathilde Steenks,

    1. Department of Medical Biochemistry,
    2. The HPB and Liver Transplant Unit, Flinders Medical Centre, and School of Medicine, Flinders University, Adelaide, South Australia, Australia;
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  • Jeroen Peters,

    1. Department of Medical Biochemistry,
    2. The HPB and Liver Transplant Unit, Flinders Medical Centre, and School of Medicine, Flinders University, Adelaide, South Australia, Australia;
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  • Willem Rademacher,

    1. Department of Medical Biochemistry,
    2. The HPB and Liver Transplant Unit, Flinders Medical Centre, and School of Medicine, Flinders University, Adelaide, South Australia, Australia;
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  • Vincent B. Nieuwenhuijs,

    1. Department of Surgery, University Medical Centre, Groningen, The Netherlands
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  • Robert T.A. Padbury,

    1. The HPB and Liver Transplant Unit, Flinders Medical Centre, and School of Medicine, Flinders University, Adelaide, South Australia, Australia;
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  • Greg J. Barritt

    1. Department of Medical Biochemistry,
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  • This article has been accepted for publication and undergone full scientific peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1111/j.1440-1746.2012.07169.x

Address for Correspondence and Proofs:
Professor Greg J. Barritt
Department of Medical Biochemistry
School of Medicine
Flinders University
GPO Box 2100
Adelaide SA 5001
Australia
Tel: +61 8 8204 4260
Fax: +61 8 8374 0139
Email: Greg.Barritt@flinders.edu.au

Abstract

Background and Aim:   Intermittent ischemia is known to promote post perfusion bile flow, and hence recovery of liver function following ischemia reperfusion of the liver. However, the mechanisms involved are not well understood. The aim of this study was to identify the step(s) in the bile acid transport pathway altered by intermittent ischemia.

Methods:  A rat model of segmental hepatic ischemia in which the bilateral median and left lateral lobes were made ischemic by clamping the blood vessels was employed. Indocyanine green (ICG), infrared spectroscopy, and compartmental kinetic analysis, were used to indirectly monitor the movement of bile acids across hepatocytes in situ. Rates of bile flow were measured gravimetrically.

Results:  In control livers (not subjected to ischemia), the movement of ICG from the blood to bile fluid could be described by a three compartment model comprised of the blood, a rapidly-exchangeable compartment, and the hepatocyte cytoplasmic space. In livers subjected to continuous clamping, the rates of ICG uptake to the liver, and outflow from the liver, were greatly reduced compared with those in control livers. Intermittent clamping (three episodes of 15 min clamping) compared with continuous clamping substantially increased the rate of ICG uptake from the blood but had less effect on the rate of ICG outflow from hepatocytes.

Conclusions:   It is concluded that intermittent ischemia promotes post reperfusion bile flow in the early phase of ischemia reperfusion injury principally by enhancing the movement of bile acids from the blood to hepatocytes.

© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

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