The Cardiome Project. An integrated view of cardiac metabolism and regional mechanical function.

The goal, to develop a functioning three-dimensional computational model of the excitation, metabolism and contraction of the heart within three years, is one of the beginnings for the Cardiome Project. Our first stage will not be likely to provide highly accurate prediction of physiological behavior in general, but will be focussed so that it is adequate for at least three specific purposes: response to regional flow reduction, response to heart rate changes, and response to increased metabolic drive. We would like to make the model visualizable by three-dimensional viewing, with cross-sectional and transparency viewing approaches, illustrate the fiber directions, the arteries, the deformation with contraction and images of regional functions such as oxygen consumption, preejection strain, or lactate concentration. The display techniques developed by Hunter et al. and by McCulloch et al. would be excellent for such demonstration and teaching purposes, and should be attractive enough for public display. The Physiome Project is underway now, with growing government and private support. Now we are going from the era of molecular biology, led by the Genome Project, into a new era of integrative biology. The goal is to understand biology so deeply and so broadly that predictions about interventions can be made. Methods of experimentation and of diagnosis are critical to acquiring the data, and therefore in making the prediction, and so all aspects of our Society's efforts and interests are relevant to undertaking this grand challenge.

[1]  Peter Hunter,et al.  Theory of heart , 1991 .

[2]  M. Kushmerick,et al.  Creatine Kinase Equilibration Follows Solution Thermodynamics in Skeletal Muscle. , 1995, The Journal of Biological Chemistry.

[3]  R. Brandenburg,et al.  Cardiology: Fundamentals and practice , 1987 .

[4]  J B Bassingthwaighte,et al.  Regional Distribution of Diffusible Tracers and Carbonized Microspheres in the Left Ventricle of Isolated Dog Hearts , 1973, Circulation research.

[5]  Terry Gaasterland,et al.  The metabolic pathway collection from EMP: the enzymes and metabolic pathways database , 1996, Nucleic Acids Res..

[6]  J. Keizer,et al.  Minimal model of beta-cell mitochondrial Ca2+ handling. , 1997, The American journal of physiology.

[7]  A D McCulloch,et al.  Regional left ventricular epicardial deformation in the passive dog heart. , 1989, Circulation research.

[8]  K. Kroll,et al.  Open-system kinetics of myocardial phosphoenergetics during coronary underperfusion. , 1997, The American journal of physiology.

[9]  Denis Noble,et al.  The development of mathematical models of the heart , 1995 .

[10]  James B. Bassingthwaighte,et al.  Whole organ approaches to cellular metabolism : permeation, cellular uptake, and product formation , 1998 .

[11]  D Garfinkel,et al.  Computer simulation of energy metabolism in anoxic perfused rat heart. , 1977, The American journal of physiology.

[12]  J B Bassingthwaighte,et al.  Regional myocardial flow and capillary permeability-surface area products are nearly proportional. , 1994, The American journal of physiology.

[13]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation. , 1994, Circulation research.

[14]  G S Kassab,et al.  Morphometry of pig coronary arterial trees. , 1993, The American journal of physiology.

[15]  L. Glass,et al.  Theory of heart : biomechanics, biophysics, and nonlinear dynamics of cardiac function , 1991 .

[16]  E. vanBavel,et al.  Branching patterns in the porcine coronary arterial tree. Estimation of flow heterogeneity. , 1992, Circulation research.

[17]  P. Hunter,et al.  Tissue remodeling with micro-structurally based material laws. , 1997, Advances in experimental medicine and biology.

[18]  F. Prinzen,et al.  A model approach to the adaptation of cardiac structure by mechanical feedback in the environment of the cell. , 1995, Advances in experimental medicine and biology.

[19]  T. A. Bronikowski,et al.  A mathematical analysis of the influence of perfusion heterogeneity on indicator extraction , 1980 .

[20]  E. Homsher,et al.  Regulation of the cross-bridge transition from a weakly to strongly bound state in skinned rabbit muscle fibers. , 1995, The American journal of physiology.

[21]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. , 1994, Circulation research.

[22]  Donald M. Bers,et al.  Excitation-Contraction Coupling and Cardiac Contractile Force , 2001, Developments in Cardiovascular Medicine.

[23]  Hartmut Bossel,et al.  Modeling and simulation , 1994 .

[24]  M. Kushmerick,et al.  Separate measures of ATP utilization and recovery in human skeletal muscle. , 1993, The Journal of physiology.

[25]  P. Hunter,et al.  Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog. , 1995, The American journal of physiology.

[26]  M. Kushmerick,et al.  Effect of physiological ADP concentrations on contraction of single skinned fibers from rabbit fast and slow muscles. , 1995, The American journal of physiology.

[27]  S Sideman,et al.  Coupling calcium binding to troponin C and cross-bridge cycling in skinned cardiac cells. , 1994, The American journal of physiology.

[28]  S Sideman,et al.  Effect of cellular inhomogeneity on cardiac tissue mechanics based on intracellular control mechanisms. , 1996, The American journal of physiology.

[29]  J. Bassingthwaighte,et al.  Role of Capillary Endothelial Cells in Transport and Metabolism of Adenosine in the Heart: An Example of the Impact of Endothelial Cells on Measures of Metabolism , 1998 .

[30]  J. Bassingthwaighte FRACTAL VASCULAR GROWTH PATTERNS. , 1992, Acta stereologica.

[31]  J B Bassingthwaighte,et al.  Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart. , 1986, The American journal of physiology.

[32]  J. Bassingthwaighte,et al.  Modeling [15O]oxygen tracer data for estimating oxygen consumption. , 1996, The American journal of physiology.

[33]  M J Kushmerick,et al.  Activity of creatine kinase in a contracting mammalian muscle of uniform fiber type. , 1994, Biophysical journal.

[34]  D. Noble,et al.  Modeling of internal pH, ion concentration, and bioenergetic changes during myocardial ischemia. , 1997, Advances in experimental medicine and biology.

[35]  M van Bilsen,et al.  Growth and hypertrophy of the heart: towards an understanding of cardiac specific and inducible gene expression. , 1993, Cardiovascular research.

[36]  F W Prinzen,et al.  Adaptation of cardiac structure by mechanical feedback in the environment of the cell: a model study. , 1994, Biophysical journal.

[37]  A. McCulloch,et al.  Non-homogeneous analysis of three-dimensional transmural finite deformation in canine ventricular myocardium. , 1991, Journal of biomechanics.

[38]  Natalia Ivanova,et al.  The metabolic pathway collection: an update , 1997, Nucleic Acids Res..

[39]  End-systolic pressure-volume relationship and intracellular control of contraction. , 1996, The American journal of physiology.

[40]  F. Plum Handbook of Physiology. , 1960 .

[41]  J B Bassingthwaighte,et al.  Molecular and particulate depositions for regional myocardial flows in sheep. , 1990, Circulation research.

[42]  James B. Bassingthwaighte,et al.  Whole Organ Approaches to Cellular Metabolism , 1998, Springer New York.

[43]  D. Martyn,et al.  Calcium regulation of tension redevelopment kinetics with 2-deoxy-ATP or low [ATP] in rabbit skeletal muscle. , 1998, Biophysical journal.

[44]  K. Kroll,et al.  Downregulation of 5'-nucleotidase in rabbit heart during coronary underperfusion. , 1998, American journal of physiology. Heart and circulatory physiology.

[45]  A McCulloch,et al.  Computational biology of the heart: from structure to function. , 1998, Progress in biophysics and molecular biology.

[46]  Vasilis Z. Marmarelis,et al.  Overview of NIH-Funded Biomedical Modeling and Simulation Resources , 1994 .

[47]  P. Hunter,et al.  Laminar structure of the heart: a mathematical model. , 1997, The American journal of physiology.

[48]  Rafael Beyar,et al.  Analytical and Quantitative Cardiology , 2012, Advances in Experimental Medicine and Biology.

[49]  J B Bassingthwaighte,et al.  Toward modeling the human physionome. , 1995, Advances in experimental medicine and biology.

[50]  D DiFrancesco,et al.  A model of cardiac electrical activity incorporating ionic pumps and concentration changes. , 1985, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[51]  G. W. Beeler,et al.  Reconstruction of the action potential of ventricular myocardial fibres , 1977, The Journal of physiology.

[52]  Y Rudy,et al.  The Vulnerable Window for Unidirectional Block in Cardiac Tissue: , 1995, Journal of cardiovascular electrophysiology.

[53]  N. Simionescu,et al.  The Cardiovascular System , 1983 .

[54]  D. Stepp,et al.  Adenosine kinetics in canine coronary circulation. , 1996, The American journal of physiology.

[55]  E. Reid CHAPTER 5 – Carbohydrate and Fatty Acid Metabolism , 1965 .

[56]  J B Bassingthwaighte,et al.  Regional myocardial flow heterogeneity explained with fractal networks. , 1989, The American journal of physiology.

[57]  R. Beyar,et al.  Molecular and subcellular cardiology : effects of structure and function , 1995 .

[58]  J B Bassingthwaighte,et al.  Fractal 15O-labeled water washout from the heart. , 1995, Circulation research.

[59]  S Sideman,et al.  Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model. , 1994, The American journal of physiology.

[60]  E M Chance,et al.  Calculation of Absolute Metabolic Flux and the Elucidation of the Pathways of Glutamate Labeling in Perfused Rat Heart by 13C NMR Spectroscopy and Nonlinear Least Squares Analysis (*) , 1995, The Journal of Biological Chemistry.

[61]  Y. Rudy,et al.  Cardiac excitation: an interactive process of ion channels and gap junctions. , 1997, Advances in experimental medicine and biology.