HEPATIC REMOVAL OF 2 FRACTIONS OF INDOCYANINE GREEN AFTER BOLUS INJECTION IN ANESTHETIZED PIGS

In the anesthetized pig, we studied the kinetics after intravenous bolus injection of two fractions of indocyanine green (ICG): the genuine ICG(g) (95-99% of total) and a degradation product, ICG(dp) (1-5%). Plasma concentrations were followed in the carotid artery and a hepatic vein. ICG(g) disappearance curves (n = 7) were biexponential with rate constants alpha = 0.189 +/- 0.021 min(-1) and beta = 0.0356 +/- 0.0061 min(-1). The hepatic extraction fraction was constant with time. A detailed mathematical analysis showed this to be in disagreement with the conventional assumption that the biexponential plasma disappearance curve is a result of backflux from the liver storage to plasma. In contrast, our observations were predicted by an alternative model assuming temporary extrahepatic, extravasal redistribution during first-order, one-way hepatic uptake. Nevertheless, when a large bolus of sulfobromophthalein (BSP) was injected 20 min after ICG, a net backflux of ICG could be demonstrated, presumably due to countertransport. Thus a sufficient description of ICG(g), kinetics must include the complex kinetic behavior of the hepatic membrane carrier involved. Mass spectrometry suggested that ICG(dp), is formed by two ICG(g) molecules. Plasma elimination of ICG(dp) was slower (alpha = 0.0094 +/- 0.0007 min(-1)). Analysis of the bile after bolus injection (n = 2) of ICG(dp) revealed two possible metabolites of ICG(dp) that were not found in urine. Since BSP injection did not alter the ICG(dp) disappearance curve, ICG(dp) is probably not taken up by the same hepatic membrane carrier as ICG(g).