Sequestered Tracer Outflow Recovery in Multiple Indicator Dilution Experiments

Abstract

The rapid, single injection, multiple indicator dilution technique has been, with suitable modeling of hepatic venous outflow curves, the standard approach for quantitative kinetic assessment of tracer cell entry and intracellular sequestration in the steady state, both in the in situ and the isolated perfused liver. Analysis of the underlying system yields, for a substance sequestered within liver cells, identical theoretical expressions for expected cumulative tracer fractional recovery and the steady–state fractional outflow recovery of the bulk substance whose behavior is being traced. Luxon and Forker (Am. J. Physiol. 1982; 243:G76-G89) pointed out that experimental cumulative tracer fractional recovery must match the value predicted by use of fitted model parameters in the theoretical recovery expression, and that this agreement must be regarded as the hallmark of successful fitting and modeling. Their attempts to demonstrate this agreement, by use of previously published data, were unsuccessful; this led them to question whether previous model analyses were valid. To reexamine the question we, therefore, analyzed three sets of data, on bilirubin, free fatty acid and galactose uptake, including those they had previously analyzed. We found excellent agreement between experimentally determined cumulative tracer recovery and theoretically predicted recovery. The theoretical recovery expression, now validated experimentally, provides a direct way of using fitted parameters for the rapid calculation of outflow recovery, which should prove generally useful in this area of kinetics. Demonstration of the expected agreement, moreover, restores confidence in the self–consistency of procedures used in the past to analyze multiple indicator dilution data.