Assessment of methods for improving tracer estimation of substrate
rate of appearance under non-steady state conditions..
Gastaldelli, A., A. R. Coggan, and R. R. Wolfe.
Metabolism Unit, Shriners Burns Institute and University of Texas
Medical Branch, Galveston, TX 77550-2725 and *Institute of Clinical
Physiology, National Research Council, Pisa, Italy 56100
APStracts 6:0282A, 1999.
The most common approach for estimating substrate rate of appearance
(Ra) is to use the single pool model first proposed by Steele. To
overcome the model error during highly non-steady state conditions,
due to the assumption of a constant volume of distribution, V, two
strategies have been proposed: 1) use of a variable tracer infusion
rate to minimize tracer-to-tracee ratio (TTR) variations (fixed
-volume approach) or 2) use of two tracers of the same substrate with
one infused at constant rate and the other at a variable rate
(variable-volume approach or Issekutz_s approach). 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-steady
state condition created by a constant infusion of epinephrine (50
ng/kg/min) with the traditional approach of Steele, which uses a
constant infusion and fixed volume. The results showed that for both
glucose and glycerol the estimates of Ra obtained with the constant
and the variable tracer infusion rate and the Steele equation were
comparable. The variable tracer infusion approach was less sensitive
to the choice of V in estimating Ra for both glycerol and glucose,
although the advantage of changing the tracer infusion rate was
greater for glucose than for glycerol. The Issekutz model showed
instability when the ratio TTR1/TTR2 approaches a constant value, and
the model is more sensitive to measurement error than the constant
volume model for both glucose and glycerol. We conclude that the one
-tracer constant-infusion technique is sufficient in most cases for
glycerol, whereas the one-tracer variable infusion technique is
preferable for glucose. Reasonable values for glucose Ra can be
obtained with the constant-infusion technique if a volume of
distribution of 145 ml/kg is used.
Received 20 April 1998; accepted in final form 15 June 1999.
APS Manuscript Number A349-8.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999