Research Themes:
Instrumentation, Imaging and Image-Guided Therapy
Systems and Quantitative Biology

Education

M.D., University of Toronto, 1955
Ph.D. (physiology), Mayo Graduate School of Medicine, 1964

Research Interests

• Cardiovascular mass transport
• Cardiac metabolism
• Simulation
• PET imaging
• Fractal physiology
• Physiome project
• Large scale systems modeling and analysis

Contact Information

Bioengineering - UW College of Engineering
University of Washington
Box 355061
William H. Foege Building N210G, Room 310F
Phone: 206-685-2012
Fax: 206-685-2651
E-mail
Lab Web site

Research Description

Understanding the relationships among different cell types within an organ requires integration of observations at the subcellular level, and on cells, organs, and the whole organism. In my laboratory the main focus is on the heart, but we also study liver, lung, and skeletal muscle. One program concerns the kinetics of energy metabolism, ATP, and adenosine and its metabolic products in endothelial and muscle cells. At times of stress, such as during oxygen deprivation or low flow, ATP is broken down, and adenosine concentration rises dramatically, causing vasodilation. We use multiple radioactive tracers simultaneously to measure reactions of adenosine and its metabolites and to determine their rates of transport across membranes. Models describe the kinetics in a precise way, allowing us to understand the regulation.

A second program concerns the spatial distribution of blood flow in the heart and its temporal fluctuation. Obstruction of large coronary arteries is partially compensated for by vasodilation in smaller arterioles. Fractal statistics are useful for characterizing the spatial variation in flow; branching of the vascular tree is fractal. Chaotic dynamics of arterial diameters appear due to cellular and biochemical cycling.

A third program, using PET imaging, allows us to appraise cellular metabolism in vivo and study regional myocardial blood flows and metabolism together. Tracers labeled with positrons are injected to give sequences of images. The regional concentrations change with time and the data are then analyzed via models for endothelial cell and cardiac cell metabolism.

A National Simulation Resource Facility for Circulatory Mass Transport and Exchange supports the modeling analyses. We develop models and numerical techniques and new methods for optimizing the parameters of model solutions to fit data from PET images or other laboratory studies. The long range goal is to provide clinical cardiologists with tools to link various aspects of cardiac physiology and disordered functions.

Dr. Bassingthwaighte is the originator of the Human Physiome Project, a large-scale international program for developing databasing and biological systems modeling for understanding genomic and pharmaceutic effects on human physiology. His program is highly collaborative, involving co-investigators at a dozen U.S. universities, several in Europe, and in 14 departments at the University of Washington. Some of these are involved in the Physiome Project, in particular the Cardiome Project. The Cardiome Project, to define a functional heart in mathematical terms, extends from the biochemistry and the signalling, to the mechanics and energetics of the three-dimensional visualizable heart.

Selected Publications

• Kellen MR and Bassingthwaighte JB. An integrative model of coupled water and solute exchange in the heart. Am J Physiol Heart Circ Physiol 285: H1303-H1316, 2003.
• Kellen MR and Bassingthwaighte JB. Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285: H1317-H1331, 2003.
• Bassingthwaighte JB. Compound delivery and local blood flows. In: Molecular Nuclear Medicine, edited by Feinendegen LE, Shreeve WW, Eckelman WC, Bahk YW, and Wagner HN Jr. Berlin Heidelberg New York: 2003, p. 171-198.
• Bassingthwaighte JB. The macro-ethics of genomics to health: The Physiome Project. Comptes Rendus Biologies de l'Academie des sciences francaise 326: 1105-1110, 2003.
• Wang CY and Bassingthwaighte JB. Blood flow in small curved tubes. J Biomech Eng 125: 910-914, 2003.
• Vinnakota K and Bassingthwaighte JB. Myocardial density and composition: A basis for calculating intracellular metabolite concentrations. Am J Physiol Heart Circ Physiol (In press Dec 03)
• Bassingthwaighte JB and Vinnakota KC. The computational integrated myocyte. A view into the virtual heart.. In: Modeling in Cardiovascular Systems, edited by S. Sideman and R. Beyar. 2003. (In press Nov 03)