Systemic modelling of human bioenergetics and blood circulation.

This work reviews the main aspects of human bioenergetics and the dynamics of the cardiovascular system, with emphasis on modelling their physiological characteristics. The methods used to study human bioenergetics and circulation dynamics, including the use of mathematical models, are summarised. The main characteristics of human bioenergetics, including mitochondrial metabolism and global energy balance, are first described, and the systemic aspects of blood circulation and related physiological issues are introduced. The authors also discuss the present status of studies of human bioenergetics and blood circulation. Then, the limitations of the existing studies are described in an effort to identify directions for future research towards integrated and comprehensive modelling. This review emphasises that a multi-scale and multi-physical approach to bioenergetics and blood circulation that considers multiple scales and physiological factors are necessary for the appropriate clinical application of computational models.

[1]  James B. Bassingthwaighte,et al.  A computational model of oxygen transport from red blood cells to mitochondria , 2002, Comput. Methods Programs Biomed..

[2]  Eun Bo Shim,et al.  Mitochondrial dysfunction and metabolic syndrome-looking for environmental factors. , 2010, Biochimica et biophysica acta.

[3]  C. Navas,et al.  Temperature effects on energy metabolism: a dynamic system analysis , 2002, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[4]  Daniel A. Beard,et al.  A Biophysical Model of the Mitochondrial Respiratory System and Oxidative Phosphorylation , 2005, PLoS Comput. Biol..

[5]  R. Moreno-Sánchez,et al.  Heart metabolic disturbances in cardiovascular diseases. , 2003, Archives of medical research.

[6]  M. Runge,et al.  Mitochondrial Dysfunction in Atherosclerosis , 2007, Circulation research.

[7]  James H Brown,et al.  Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Wallace Mitochondria as Chi , 2008, Genetics.

[9]  Chi-Ngon Nguyen,et al.  The benefits of using Guyton's model in a hypotensive control system , 2008, Comput. Methods Programs Biomed..

[10]  Peter J Hunter,et al.  Modeling total heart function. , 2003, Annual review of biomedical engineering.

[11]  A. Noma,et al.  A new integrated method for analyzing heart mechanics using a cell-hemodynamics-autonomic nerve control coupled model of the cardiovascular system. , 2008, Progress in biophysics and molecular biology.

[12]  K. B. Saunders Oscillations of arterial CO2 tension in a respiratory model: some implications for the control of breathing in exercise. , 1980, Journal of theoretical biology.

[13]  E. Clementi,et al.  Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide , 2003, Science.

[14]  D. Noble Systems biology and the heart. , 2006, Bio Systems.

[15]  Stephen Coombes,et al.  Mathematical Modeling of Glucose Homeostasis and Its Relationship With Energy Balance and Body Fat , 2009, Obesity.

[16]  Eun Bo Shim,et al.  Physiome and Sasang Constitutional Medicine. , 2008, The journal of physiological sciences : JPS.

[17]  J Strackee,et al.  Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. , 1987, The American journal of physiology.

[18]  R. Winslow,et al.  An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. , 2003, Biophysical journal.

[19]  L Garby,et al.  Prediction of body weight changes caused by changes in energy balance , 2002, European journal of clinical investigation.

[20]  T. G. Coleman,et al.  Circulation: overall regulation. , 1972, Annual review of physiology.

[21]  R. Wiesner,et al.  Stimulation of Mitochondrial Gene Expression and Proliferation of Mitochondria Following Impairment of Cellular Energy Transfer by Inhibition of the Phosphocreatine Circuit in Rat Hearts , 1999, Journal of bioenergetics and biomembranes.

[22]  G. Saidel,et al.  Lactate metabolism during exercise: analysis by an integrative systems model. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[23]  G. Saidel,et al.  Multi-Scale Computational Model of Fuel Homeostasis During Exercise: Effect of Hormonal Control , 2006, Annals of Biomedical Engineering.

[24]  K. Uğurbil,et al.  Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy. , 1997, Circulation.

[25]  V. Víctor,et al.  Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. , 2009, Current medicinal chemistry.

[26]  Ranjan K Dash,et al.  Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies. , 2009, American journal of physiology. Cell physiology.

[27]  Satoshi Matsuoka,et al.  Regulation of oxidative phosphorylation in intact mammalian heart in vivo. , 2005, Biophysical chemistry.

[28]  Carson C. Chow,et al.  The Dynamics of Human Body Weight Change , 2008, PLoS Comput. Biol..

[29]  Eun Bo Shim,et al.  Computational analysis of the effect of the type of LVAD flow on coronary perfusion and ventricular afterload , 2009, The Journal of Physiological Sciences.

[30]  A. Guyton,et al.  Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models. , 1990, The American journal of physiology.

[31]  Guido Avanzolini,et al.  An integrated model of the human ventilatory control system: the response to hypoxia , 2001 .

[32]  Michael E Phelps,et al.  Systems Biology and New Technologies Enable Predictive and Preventative Medicine , 2004, Science.

[33]  K. Sahlin,et al.  Mitochondrial dysfunction in type 2 diabetes and obesity. , 2008, Endocrinology and metabolism clinics of North America.

[34]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[35]  Satoshi Matsuoka,et al.  Calcium-mediated coupling between mitochondrial substrate dehydrogenation and cardiac workload in single guinea-pig ventricular myocytes. , 2006, Journal of molecular and cellular cardiology.

[36]  S. Matsuoka,et al.  Simulation of ATP metabolism in cardiac excitation-contraction coupling. , 2004, Progress in biophysics and molecular biology.

[37]  B. Korzeniewski,et al.  A model of oxidative phosphorylation in mammalian skeletal muscle. , 2001, Biophysical chemistry.

[38]  Donald T. Kirkendall,et al.  The Effects of Aging and Training on Skeletal Muscle , 1998, The American journal of sports medicine.

[39]  Y. Pak,et al.  Mitochondria‐Based Model for Fetal Origin of Adult Disease and Insulin Resistance , 2005, Annals of the New York Academy of Sciences.

[40]  P. Kiberstis Mitochondria and Diabetes , 2004, Science.

[41]  J. Rice,et al.  Approximate model of cooperative activation and crossbridge cycling in cardiac muscle using ordinary differential equations. , 2008, Biophysical journal.

[42]  B. Korzeniewski,et al.  Oxygen delivery by blood determines the maximal VO2 and work rate during whole body exercise in humans: in silico studies. , 2007, American journal of physiology. Heart and circulatory physiology.

[43]  Akinori Noma,et al.  A new multi-scale simulation model of the circulation: from cells to system , 2006, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[44]  J. Costa,et al.  Systems medicine in oncology , 2008, Nature Clinical Practice Oncology.

[45]  Mauro Ursino,et al.  Interaction between carotid baroregulation and the pulsating heart: a mathematical model. , 1998, American journal of physiology. Heart and circulatory physiology.

[46]  S Heshka,et al.  Resting energy expenditure-fat-free mass relationship: new insights provided by body composition modeling. , 2000, American journal of physiology. Endocrinology and metabolism.

[47]  H. Kimura,et al.  A mathematical model of brain glucose homeostasis , 2009, Theoretical Biology and Medical Modelling.

[48]  Toshiaki Hisada,et al.  Multiphysics simulation of left ventricular filling dynamics using fluid-structure interaction finite element method. , 2004, Biophysical journal.

[49]  Satoshi Matsuoka,et al.  An in silico study of energy metabolism in cardiac excitation-contraction coupling. , 2004, The Japanese journal of physiology.

[50]  James B. Bassingthwaighte,et al.  Strategies for the Physiome Project , 2000, Annals of Biomedical Engineering.

[51]  R. Mark,et al.  Computational modeling of cardiovascular response to orthostatic stress. , 2002, Journal of applied physiology.

[52]  J. Bournat,et al.  Mitochondrial dysfunction in obesity. , 2010, Current opinion in endocrinology, diabetes, and obesity.

[53]  W. Porter,et al.  A New Model for the Body Size–Metabolism Relationship , 2010, Physiological and Biochemical Zoology.

[54]  Robert F Gilmour,et al.  Ionic mechanism of electrical alternans. , 2002, American journal of physiology. Heart and circulatory physiology.

[55]  Kevin D Hall,et al.  Computational model of in vivo human energy metabolism during semistarvation and refeeding. , 2006, American journal of physiology. Endocrinology and metabolism.

[56]  P. Mitchell Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism , 1961, Nature.

[57]  M. Ursino,et al.  Role of short-term cardiovascular regulation in heart period variability: a modeling study. , 2003, American journal of physiology. Heart and circulatory physiology.

[58]  Eun Bo Shim,et al.  Mathematical modeling of cardiovascular system dynamics using a lumped parameter method. , 2004, The Japanese journal of physiology.

[59]  J A Negroni,et al.  A cardiac muscle model relating sarcomere dynamics to calcium kinetics. , 1996, Journal of molecular and cellular cardiology.

[60]  M. Ursino,et al.  Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects , 2006, Medical and Biological Engineering and Computing.

[61]  T. G. Coleman,et al.  Quantitative Circulatory Physiology: An integrative mathematical model of human physiology for medical education , 2007, Advances in physiology education.

[62]  Roy C. P. Kerckhoffs,et al.  Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation , 2006, Annals of Biomedical Engineering.

[63]  Viatcheslav Gurev,et al.  Comparison of the effects of continuous and pulsatile left ventricular-assist devices on ventricular unloading using a cardiac electromechanics model , 2011, The Journal of Physiological Sciences.

[64]  P. Hunter,et al.  Modelling the mechanical properties of cardiac muscle. , 1998, Progress in biophysics and molecular biology.