MINIMAL COMPARTMENTAL MODEL OF CIRCULATORY MIXING OF INDOCYANINE GREEN

A model of indocyanine green (ICG) disposition from the moment of its injection in blood was developed. ICG disposition was characterized in five dogs deeply anesthetized with halothane, which decreased cardiac output and prolonged intravascular mixing. After ICG injection into the right atrium, femoral arterial blood samples were collected every 3 s for the 1st min and less frequently to 20 min. ICG concentrations were measured by high-performance liquid chromatography and modeled with SAAM 30.1. A fully identifiable recirculatory compartmental model with time delays was used to describe ICG disposition. The central blood volume averaged 23.4 ml/kg, and total blood volume averaged 78.9 ml/kg. Fifty-three percent of the cardiac output flowed through 14% of the peripheral blood volume while the remaining 47% flowed through 86% of the peripheral volume. This new model is isomorphic with a parallel channel, lumped-parameter circulation model and provides more information than stochastic, noncompartmental recirculatory pharmacokinetic techniques. This intravascular mixing model can be applied to determine the contribution of the circulation to drug distribution.