This page will look better in a graphical browser that supports web standards, but is accessible to any browser or internet device.

Served by Samwise.

Cardiac Physiome Society workshop: November 6-9, 2017 , Toronto

Tracers in physiological systems modeling

Authors: Anderson JC and Bassingthwaighte JB, 2007

Description

Metabolic events within cells are intimately linked with the external influences of substrate delivery and metabolite removal. These influences include the level of cellular activity, the local blood flow, transmembrane transport rates, and humoral and neural regulation of receptors and reaction rates. The question "What are the basic principles that the developers of tracer models should use?" evokes discussion on the scope of the modeling: an extremes is "minimal modeling", wherein one considers only the observations of the injected tracer-labelled solute itself (as in pharmacokinetics), its reaction products, or extend to its effects on the physiology (as in pharmacodynamics).
Minimal modeling can work for classification or diagnosis but, unless the model has the depth to encompass mechanisms of tracer handling, doesn't often provide an explanation. Here we advocate adherence to a broad set of principles for the design and application of models to the understanding of physiological systems: (1) consider the anatomy (a biological constraint) as an essential part of the data, (2) take into account the background physiological state of the subject (biochemical, thermodynamic constraints), (3) consider the processes that the tracer labelled solutes undergo (mechanisms of transport and reaction), (4) be obedient to the laws of physics and chemistry (conservation principles for mass, energy, charge, momentum, etc.), and (5) adhere to a set of modeling standards allowing reproducibility and dissemination of the model. A two compartment model with a binding site illustrates that recognition of the anatomic constraints would foster a better understanding of the system kinetics. Another example is to abandon the lumped compartmental representation of spatially extended capillary-tissue exchange in favor of using anatomic-based equations, thereby obtaining physically meaningful esxtimates of parameter values.

For more detailed information, see: Tracers in physiological systems modeling (pdf format):

Anderson JC and Bassingthwaighte JB: "Tracers in physiological systems modeling". In: Mathematical Modeling in Nutrition and Agriculture. Proc 9th International Conf on Mathematical Modeling in Nutrition, Roanoke, VA, August 14-17, 2006, edited by Mark D. Hanigan JN and Casey L Marsteller. Virginia Polytechnic Institute and State University, Blacksburg, VA 2007, pp 125-159.

Return to Compartmental Models Tutorial

Related Models

Models used to produce figures in Anderson JC 2007 paper.

Two compartment model discussion:

Three region serial tank and axial dispersion model discussion:

References

Bassingthwaighte JB, Yipintsoi T, and Harvey RB. Microvasculature of the dog left
ventricular myocardium. Microvasc Res 7: 229-249, 1974.

Bassingthwaighte JB, Wang CY, and Chan IS. Blood-tissue exchange via transport
and transformation by endothelial cells. Circ Res 65: 997-1020, 1989.

Bassingthwaighte JB, Chan IS, and Wang CY. Computationally efficient algorithms
for capillary convection-permeation-diffusion models for blood-tissue exchange. Ann Biomed
Eng 20: 687-725, 1992.

Bassingthwaighte JB and Vinnakota KC. The computational integrated myocyte. A
view into the virtual heart. In: Modeling in Cardiovascular Systems. Ann. New York Acad. Sci.
1015:, edited by S. Sideman and R. Beyar. 2004, p. 391-404.

Bassingthwaighte JB, Raymond GR, Ploger JD, Schwartz LM, and Bukowski TR.
GENTEX, a general multiscale model for [italic] in vivo [plain] tissue exchanges and intraorgan
metabolism. Phil Trans Roy Soc A: Mathematical, Physical and Engineering Sciences 364(1843):
1423-1442, 2006.

Beard DA, Liang S, and Qian H. Energy balance for analysis of complex metabolic
netw orks. Biophys J 83: 79-86, 2002.

Berman M. The formulation and testing of models. Ann NY Acad Sci 108: 182-194,
1963.

Chinard FP, Vosburgh GJ, and Enns T. Transcapillary exchange of water and of other
substances in certain organs of the dog. Am J Physiol 183: 221-234, 1955.
Cobelli C, Foster D, and Toffolo G. Tracer Kinetics in Biomedical research. From data to
model. Kluwer Academic/Plenum Publishers, New York, 2000.

Crone C. The permeability of capillaries in various organs as determined by the use of
the 'indicator diffusion' method. Acta Physiol Scand 58: 292-305, 1963

Dash RK and Bassingthwaighte JB. Blood HbO2 and HbCO2 dissociation curves at varied O2,
CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 32: 1676-1693, 2004.

Dash RK, Li Z, and Bassingthwaighte JB. Simultaneous blood-tissue exchange of oxygen, carbon
dioxide, bicarbonate, and hydrogen ion. Ann Biomed Eng 34: 2006.

Gorman MW, Bassingthwaighte JB, Olsson RA, and Sparks HV. Endothelial cell
uptake of adenosine in canine skeletal muscle. Am J Physiol Heart Circ Physiol 250: H482-H489,
1986.

International Commission on Radiological Protection. Basic Anatomical and Physiological Data
for Use in Radiological Protection: Reference Values. New York: Elsevier Science, 2003, 320 pp.

Kassab GS, Rider CA, Tang NJ, and Fung Y-CB. Morphometry of pig coronary arterial trees. Am
J Physiol Heart Circ Physiol 265: H350-H365, 1993.

Kuikka J, Levin M, and Bassingthwaighte JB. Multiple tracer dilution estimates of Dand
2-deoxy-D-glucose uptake by the heart. Am J Physiol Heart Circ Physiol 250: H29-H42,
1986.

Krogh A. The number and distribution of capillaries in muscles with calculations of the
oxygen pressure head necessary for supplying the tissue. J Physiol (Lond) 52: 409-415, 1919.

Li Z, Yipintsoi T, and Bassingthwaighte JB. Nonlinear model for capillary-tissue
oxygen transport and metabolism. Ann Biomed Eng 25: 604-619, 1997.

Poulain CA, Finlayson BA, and Bassingthwaighte JB. Efficient numerical methods
for nonlinear facilitated transport and exchange in a blood-tissue exchange unit. Ann Biomed Eng
25: 547-564, 1997.

Schwartz LM, Bukowski TR, Ploger JD, and Bassingthwaighte JB. Endothelial
adenosine transporter characterization in perfused guinea pig hearts. Am J Physiol Heart Circ
Physiol 279: H1502-H1511, 2000.

Vinnakota K, Kemp ML, and Kushmerick MJ. Dynamics of muscle glycogenolysis modeled
with pH time-course computation and pH dependent reaction equilibria and enzyme kinetics.
Biophys J doi:10.1529/biophys.105.073296: 1-64, 2007.

Vinnakota K and Bassingthwaighte JB. Myocardial density and composition: A basis
for calculating intracellular metabolite concentrations. Am J Physiol Heart Circ Physiol 286:
H1742-H1749, 2004.

Yipintsoi T, Scanlon PD, and Bassingthwaighte JB. Density and water content of dog
ventricular myocardium. Proc Soc Exp Biol Med 141: 1032-1035, 1972.

Key Terms

tracer, tracee, metabolic physiologic modeling, lumped compartmental versus spatially distributed systems, capillary-tissue exchange, membrane transporters, enzyme reactions, steady state versus transient states.

Acknowledgements

Please cite www.physiome.org in any publication for which this software is used and send one reprint to the address given below:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.

[This page was last modified 02Nov16, 2:20 pm.]

Model development and archiving support at physiome.org provided by the following grants: NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.