Direct measurement of hepatic indocyanine green clearance with near-infrared spectroscopy: Separate evaluation of uptake and removal

We continuously measured hepatic absorbance of indocyanine green (ICG) using near-infrared (NIR) spectroscopy after intravenous bolus injection in rabbits. Hepatic ICG concentration was obtained by subtracting out the absorbance of hemoglobin and other pigments within the liver. Two exponential rate constants, the first reflecting the dye uptake from plasma to the hepatocytes, and the second representing the dye removal from the liver by cytoplasmic transport and biliary excretion, were determined by fitting the time-course curve of hepatic ICG concentration to a two-compartment model with irreversible transfer between the two compartments, as defined by the double-exponential equation: [ICG]liver(t) = -A exp(-alpha t) + B exp(-beta t). The results showed that treatment with bilirubin, a competitive inhibitor of ICG uptake, caused a decrease in alpha. Treatment with either colchicine, which is toxic to microtubules, or with ouabain, an inhibitor of Na+,K(+)-ATPase, caused a decrease in beta. These results were compatible with the kinetic model. This new method was then used in liver-injured rabbits inflicted with hemorrhagic shock and ischemia-reperfusion, to show that the first rate constant is primarily affected by hepatic microcirculatory condition, and the second refers closely to parenchymal liver damage. In another series of partial liver ischemia-reperfusions, it was possible to simultaneously and separately monitor the ICG profiles of post-ischemic and nonischemic areas. Thus, the kinetic analysis of hepatic ICG concentration curves, as directly measured by NIR spectroscopy, led to the separate evaluation of different clearance process of ICG in the liver, suggesting the advanced utility as a comprehensive liver function test.