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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 20, 2003; DOI: 10.1124/jpet.103.058941

0022-3565/04/3081-198-205$20.00
JPET 308:198-205, 2004
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CARDIOVASCULAR

A Physiologically Based Approach for the Estimation of Recirculatory Parameters

Vangelis Karalis, Aristides Dokoumetzidis, and Panos Macheras

Laboratory of Biopharmaceutics-Pharmacokinetics, School of Pharmacy, University of Athens, Athens, Greece

Indicator dilution studies are used to provide estimates for several physiological parameters such as cardiac output as well as intra- and extravascular volumes. This study introduces a novel technique for the estimation of recirculatory parameters. A mathematical model based on a dispersion-convection partial differential equation (PDE), derived from the fractal geometry of the vascular tree and the hydrodynamics of the blood flow, is used to describe the spatiotemporal profile of tracers in the circulatory system. Initially, the equation is fitted to concentration-time (C,t) data of a tracer to derive the parameter estimates of the model equation; in a subsequent step, these estimates along with appropriate changes of the parameters of the PDE are used to generate the early concentration-time profile of a hypothetical appropriate tracer without recirculation. Thus, the area under the concentration-time curve of the first passage of the tracer is calculated and used for the estimation of various physiological parameters, including cardiac output, miscellaneous partial blood volumes, and the corresponding mean transit times. The procedure was applied successfully to literature data of various tracers from humans and dogs.

Received August 21, 2003; accepted September 23, 2003.

Address correspondence to: Dr. Panos Macheras, School of Pharmacy, University of Athens, Panepistimiopolis, Athens, 15771 Greece. E-mail: macheras{at}pharm.uoa.gr






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