Journal of Surgical Research
Volume 146, Issue 2 , Pages 164-171, 15 May 2008

Biliary-Type Cytokeratin Pattern in a Canine Isolated Perfused Liver Transplantation Model12

  • Consolato Sergi, M.D., Ph.D.

      Affiliations

    • Institute of Pathology, Innsbruck Medical University, Innsbruck, Austria
    • Department of Pediatric Pathology, University of Bristol, Bristol, United Kingdom
    • Corresponding Author InformationTo whom correspondence and reprint requests should be addressed at Institute of Pathology, Medical University of Innsbruck, Muellerstrasse 44, A-6020 Innsbruck, Austria.
    • ,
  • Wolfgang Gross, Ph.D., C.Stat.

      Affiliations

    • Department of Experimental Surgery, Heidelberg Medical University, Heidelberg, Germany
    • ,
  • Martin Mory, M.D.

      Affiliations

    • Department of Experimental Surgery, Heidelberg Medical University, Heidelberg, Germany
    • ,
  • Michael Schaefer, Ph.D.

      Affiliations

    • Department of Experimental Surgery, Heidelberg Medical University, Heidelberg, Germany
    • ,
  • Martha-Maria Gebhard, M.D., Ph.D.

      Affiliations

    • Department of Experimental Surgery, Heidelberg Medical University, Heidelberg, Germany

Received 2 February 2007 published online 09 July 2007.

Background

Ischemia-reperfusion (I/R) injury in liver transplantation units and the influence of I/R injury on bile flow dynamics is being intensely investigated in various animal models, but the expression of intracellular intermediate filaments of biliary type as an early sign of cholestasis has not been yet explored.

Methods

We studied the hepatic elimination kinetics of indocyanine green (ICG), an exclusively biliary excreted cholephilic dye, and the functional and morphological integrity of liver cells in a canine liver transplantation model following I/R. During reperfusion following cold ischemia, we evaluated the ICG excretion curves, biochemical signs of liver damage, the bile canaliculus of the hepatocytes by electron microscopy, and the expression of intermediate filaments of cytokeratin type by immunohistochemistry.

Results

Impairment of the biliary ICG excretion was directly related to ischemia time, but hepatocellular ICG uptake and bile flow rate were not significantly reduced. Liver enzymes increased as early as 6 h of ischemia and hepatocytes showed an increase of the bile canaliculus area. This was correlated to a membranous to cytoplasmatic staining of the cytoskeleton of the hepatocytes.

Conclusions

To the best of our knowledge, this is the first evidence of cholestatic changes starting early following cold ischemia in a canine isolated perfused liver transplantation model despite prompt recovery of the bile flow.

Key Words: liver transplantation, primary graft dysfunction, cholestasis, hepatocellular transport

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1 Consolato Sergi and Martin Mory contributed equally to this work.

2 Preliminary data of this paper were presented in part at the Annual Meeting of the Pathological Society of Great Britain and Ireland, Newcastle upon Tyne, United Kingdom, 4th-7th July 2005 (J Pathol Suppl July 2005).

PII: S0022-4804(07)00376-9

doi:10.1016/j.jss.2007.05.024

Journal of Surgical Research
Volume 146, Issue 2 , Pages 164-171, 15 May 2008

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