Assessment of methods for improving tracer estimation of non-steady-state rate of appearance

The most common approach for estimating substrate rate of appearance (R-a) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. (Am. J. Physiol. 187: 15-24, 1956). To ove rcome the model error during highly nan-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have be en proposed: 1) use of a variable tracer infusion rate to minimize tracer-t o-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tr acers of the same substrate with one infused at a constant rate and the oth er at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215-224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-stea dy-state condition created by a constant infusion of epinephrine (50 ng.kg( -1).min(-1)) with the traditional approach of Steele et al., which uses a c onstant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of R-a obtained with the constant and the variable t racer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating R-a for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The mo del of Issekutz et al. showed instability when the ratio TTR1/TTR2 approach es a constant value, and the model is more sensitive to measurement error t han the constant-volume model for glucose and glycerol. We conclude that th e one-tracer constant-infusion technique is sufficient in most cases for gl ycerol, whereas the one-tracer variable-infusion technique is preferable fo r glucose. Reasonable values for glucose R, can be obtained with the consta nt-infusion technique if V = 145 ml/kg.