Biliary-type cytokeratin pattern in a canine isolated perfused liver transplantation model.

Abstract

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.