The goals are (1) to develop a more complete oxygen transport and metabolism model, namely, incorporating more general nonlinear binding of oxygen to hemoglobin and myoglobin, incorporating effect of pH and CO2, and incorporating mitochondria into our current nonlinear oxygen model; (2) to integrate the oxygen model with other models for substrate transport and metabolism and for cardiac energetics; and (3) to expand the applications of the oxygen model. The first goal requires better understanding of non-equilibrium binding of oxygen to hemoglobin and myoglobin under varied physiological conditions, the transport of CO2, and mitochondria distribution and kinetics. The second goal is for integrating specific blood-tissue exchange models at a higher level. Currently, we are developing a comprehensive model for cardiac purine metabolism. The integration of the oxygen model and the purine model, combining with a finite-element model for cardiac mechanics, will help the understanding of the relationships among cardiac substrate transport, ATP utilization, and cardiac contractile functions during different physiological and pathological conditions. For the third goal, we are ready for some simulation studies on the BOLD technique in which the non-equilibrium binding of oxygen to hemoglobin and myoglobin, and time-varying blood flow, blood volume and metabolic activity are accounted for in the oxygen model.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001243-18
Application #
6119758
Study Section
Project Start
1998-12-16
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Bassingthwaighte, James B; Butterworth, Erik; Jardine, Bartholomew et al. (2012) Compartmental modeling in the analysis of biological systems. Methods Mol Biol 929:391-438
Dash, Ranjan K; Bassingthwaighte, James B (2010) Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 38:1683-701
Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20
Dash, Ranjan K; Bassingthwaighte, James B (2006) Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion. Ann Biomed Eng 34:1129-48
Dash, Ranjan K; Bassingthwaighte, James B (2004) Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 32:1676-93
Kellen, Michael R; Bassingthwaighte, James B (2003) Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285:H1317-31
Kellen, Michael R; Bassingthwaighte, James B (2003) An integrative model of coupled water and solute exchange in the heart. Am J Physiol Heart Circ Physiol 285:H1303-16
Wang, C Y; Bassingthwaighte, J B (2001) Capillary supply regions. Math Biosci 173:103-14
Swanson, K R; True, L D; Lin, D W et al. (2001) A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly. Am J Pathol 158:2195-9
Swanson, K R; Alvord Jr, E C; Murray, J D (2000) A quantitative model for differential motility of gliomas in grey and white matter. Cell Prolif 33:317-29

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