Hepatocyte Concentrations of Indocyanin Green (ICG) Reflects Transfer Rates Across Membrane Transporters

Article Article scientifique Article Hepatocyte Concentrations of Indocyanin Green (ICG) Reflects Transfer Rates Across Membrane Transporters eng 2017 author Cusin Fabien 690117 author Azevedo Liliana 514033 author Bonnaventure Pierre 769149 author Desmeules Jules Alexandre 73542 author Daali Youssef 46042 author Pastor Catherine 0000-0002-1551-3824 128329 171-178 10.1111/bcpt.12671 27623731 1742-7835 Peroperative imaging with indocyanin green (ICG) is developing to increase safety in dissecting anatomical structures during hepatobiliary surgery. Images obtained with the fluorescence camera rely on concentrations measured in liver regions of interest. However, how ICG sinusoidal uptake and hepatocyte elimination rates generate ICG hepatocyte concentrations is largely unknown. To investigate such issue and better understand the role of membrane transporters in generating ICG hepatocyte concentrations, we perfused ICG in livers isolated from normal livers. Whether the well-known transporter inhibitor rifampicin modifies hepatocyte ICG concentrations was also studied. The dye has a very high and constant extraction ratio (96%) into hepatocytes. This persistent high extraction ratio generates a huge uphill concentration gradient across the sinusoidal membrane: from 5 μM (sinusoids) to 1600 μM (liver). When inside hepatocytes, ICG has low hepatocyte elimination (7 nmol/min) and liver concentrations do not decrease much over time. Moreover, the tiny hepatocyte ICG efflux is mainly due to ICG return back to sinusoids (90%). Rifampicin slightly inhibits ICG uptake into hepatocytes and when inside hepatocytes blocks ICG efflux into bile canaliculi. In contrast, it increases ICG efflux back to sinusoids with significant decrease in ICG liver concentrations. Imaging with ICG in the peroperative period reflects the high hepatocyte concentrations and relies on the high extraction ratio across hepatocyte sinusoidal membrane. Although ICG concentrations are low in bile ducts, they are adequate for a good visualisation and avoid bile duct injury. This article is protected by copyright. All rights reserved. Dewey 615 Dewey 616.0757 31 Section des sciences pharmaceutiques 17 62 Département de radiologie et informatique médicale 227 false 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 1280 Pharmaco-omiques et médecine de précision 1003 396 Pharmacologie et imagerie du foie 664 Basic & clinical pharmacology & toxicology 120 2 2c284dbb-f74e-4ee4-bc27-28d4796c0e8a Article (Published version) Restricted BCRP.pdf 266818 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale

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Hepatocyte Concentrations of Indocyanin Green (ICG) Reflects Transfer Rates Across Membrane Transporters	Basic & clinical pharmacology & toxicology			2017	548	3

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Azevedo, Liliana