Bicarbonate kinetics in humans: identification and validation of a three
-compartment model.
Saccomani, M. P., R. C. Bonadonna, E. Caveggion, R. A. Defronzo, C. Cobelli.
Department of Electronics and Informatics, University of Padova, 35131
Padova, Italy, Division of Metabolic Diseases, University of Verona, 37124,
Verona, Italy, Division of Diabetes, University of Texas Health Science
Center, San Antonio, Texas 78284, USA
APStracts 2:0013E, 1995.
A model of bicarbonate kinetics is crucial to a correct interpretation of
experiments for measuring oxidation in vivo of carbon-labelled compounds. The
aim of this paper is to develop a compartmental model of bicarbonate kinetics
in man from tracer data by devoting particular attention to model
identification and validation. The data base consisted in impulse dose
studies of [ C]-bicarbonate in 9 normal subjects. The decay curve of
specific activity of CO in the expired air, sa, was frequently sampled for 4
-7 hours. In addition the endogenous production of CO, V, was measured by
indirect calorimetry. A model of data, i.e. an exponential model, analysis of
the decay curves of sa showed first that three compartments are necessary and
sufficient to describe bicarbonate tracer kinetics. Compartmental models were
then used as models of system. To correctly describe the input-output
configuration, the labelled CO flux in the expired air, f (=sa QV ), has been
used as measurement variable in tracer model identification. A mamillary
three compartment model with both a respiratory and a non-respiratory loss
has been studied. While good evidence exists that the respiratory loss takes
place in the central compartment, uncertainty exists on whether the non
-respiratory loss is taking place in the central or in one of the two
peripheral compartments. Thus three competing tracer models were considered.
By using a model-independent analysis of data, based on the body activity
variable, to calculate the mean residence time in the system, we have been
able to validate a specific model structure, i.e. with the two irreversible
losses both taking place in the central compartment. This validated tracer
model has then been used to quantitate bicarbonate masses in the system.
Since uncertainty exists on where endogenous production enters the system,
lower and upper bounds of masses of bicarbonate in the body are derived.
Received 10 August 1993; accepted in final form 18 January 1995.
APS Manuscript Number E300-3.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.