[Flow rates in the isolated perfused rat liver by pulse labeling with radioactive substrates and mathematical analysis of the wash-out kinetics].

The multiple indicator dilution technique (Goresky and Bach) is critically evaluated and its application to the isolated, hemoglobin-free perfused rat liver is described. From the results of pulse labelling experiments using indicator substances for the total aqueous space of the liver ([3H]water and [14C]urea) an for the extracellular space ([14C]sucrose, [3H]-inulin and [3H]dextrane), it is concluded that the mathematical model of the liver in situ according to Goresky and Bach is sufficient to also describe the hemodynamics of the isolated liver perfused with a saline solution. The data indicate that the multiple indicator dilution technique in combination with the available mathematical basis is applicable to the study of transport across the liver cell membrane. The method, however, is restricted to compounds which are metabolized very slowly, such as D-lactate. A possible extension of this method to metabolic processes is discussed in view of pulse labelling experiments with [3H]-and [1-14C]L-lactate. Since the involvement of metabolism in the available mathematical model is not differentiated and the release of products is not taken into consideration, the method in its present state is not applicable to studies of metabolism. Moreover, even the parameters of transport derived by this technique are of limited value, when the transported compounds are rapidly metabolized by reversible reactions. Despite these uncertainties, the present data indicate that the transport of L-lactate is ten times faster than that of D-lactate.