Experimental Validation of Nonsteady Rate Measurements using a Tracer Infusion Method and Inulin as Tracer and Tracee

Abstract

In 1959, Steele (Ann. N.Y. Acad. Sci. 82, 420–430) suggested a method for measuring the rates of appearance (Ra) and of disappearance (Rd) of a metabolite in an intact system under conditions when Ra and Rd were changing with time. Steele's method involved modelling the system by a one-compartment model whose effective volume was assumed. To overcome the problem of assuming an effective volume, a model consisting of two compartments rather than one has been postulated. While no distribution volume need now be assumed, a preliminary steady state experiment is required for identification of the coefficients governing exchange of material between the two compartments.In five conscious dogs 14C-hydroxymethyl inulin (tracer) was infused at a constant rate, while unlabelled inulin (tracee) was infused at varying predetermined rates and the plasma concentrations of both were measured. These were then fitted by a series of smoothly joined polynomials. When the calculated rates of appearance of unlabelled inulin were compared with the actual rates, equally good results were obtained with the one-compartment (using the best effective volume) and the two-compartment models. The calculated values of Rd and of the clearance of inulin were not validated experimentally, but their validity is likely since the equations for Rd and Ra are related, and the Ra component has been validated. The identity of unlabelled inulin and the 14C-hydroxymethyl inulin species was ascertained by gel filtration, and by the identity of their in vivo kinetics.