BICARBONATE KINETICS IN HUMANS - IDENTIFICATION AND VALIDATION OF A 3-COMPARTMENT MODEL

A model of bicarbonate kinetics is crucial to a correct interpretation of experiments for measuring oxidation in vivo of carbon-labeled comp ounds. The aim of this study is to develop a compartmental model of bi carbonate kinetics in humans from tracer data by devoting particular a ttention to model identification and validation. The data base consist ed of impulse-dose studies of C-14-labeled bicarbonate in nine normal subjects. The decay curve of specific activity of CO2 in expired air ( sa(CO2)(R)) was frequently sampled for 4-7 h. In addition, endogenous production of CO2, V-CO2, was measured by indirect calorimetry. A mode l of data, i.e., an exponential model, analysis of decay curves of sa( CO2)(R) showed first that three compartments are necessary and suffici ent to describe bicarbonate tracer kinetics. Compartmental models were then used as models of system. To correctly describe the input-output configuration, labeled CO2 flux in the expired air, phi(CO2)(R), (= s a(CO2)(R) . V-CO2), has been used as measurement variable in tracer mo del identification. A mammillary three-compartment model with a respir atory and a nonrespiratory loss has been studied. Whereas there is goo d evidence that respiratory loss takes place in the central compartmen t, whether nonrespiratory loss is taking place in the central compartm ent or in one of the two peripheral compartments is uncertain. Thus th ree competing tracer models were considered. Using a model-independent analysis of data, based on the body activity variable, to calculate m ean residence time in the system, we have been able to validate a spec ific model structure, i.e., with the two irreversible losses taking pl ace in the central compartment. This validated tracer model was then u sed to quantitate bicarbonate masses in the system. Because there is u ncertainty about where endogenous production enters the system, lower and upper bounds of masses of bicarbonate in the body are derived.