An integrated mathematical model of the human cardiopulmonary system: model development.

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics.

[1]  Mauro Ursino,et al.  An integrated mathematical model of the human cardiopulmonary system: model validation under hypercapnia and hypoxia. , 2016, American journal of physiology. Heart and circulatory physiology.

[2]  James Duffin,et al.  Model Validation and Control Issues in the Respiratory System , 2013 .

[3]  M. Khoo,et al.  Modeling the Autonomic and Metabolic Effects of Obstructive Sleep Apnea: A Simulation Study , 2012, Front. Physio..

[4]  Mauro Ursino,et al.  Transient respiratory response to hypercapnia: Analysis via a cardiopulmonary simulation model , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[5]  M. Manivannan,et al.  Cardiopulmonary model to study interaction hemodynamics in Muller maneuver , 2011 .

[6]  Willem van Meurs,et al.  Modeling and Simulation in Biomedical Engineering: Applications in Cardiorespiratory Physiology , 2011 .

[7]  R. Hester,et al.  HumMod: A Modeling Environment for the Simulation of Integrative Human Physiology , 2011, Front. Physio..

[8]  B. Fuhrman.  Chapter 26 – Cardiopulmonary Interactions , 2011 .

[9]  Limei Cheng,et al.  An integrative model of respiratory and cardiovascular control in sleep-disordered breathing , 2010, Respiratory Physiology & Neurobiology.

[10]  Mauro Ursino,et al.  A comprehensive cardiopulmonary simulation model for the analysis of hypercapnic respiratory failure , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[11]  J. Karemaker,et al.  Last word on point:counterpoint: respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism. , 2009, Journal of applied physiology.

[12]  C. Steinback,et al.  Hypercapnic vs. hypoxic control of cardiovascular, cardiovagal, and sympathetic function. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[13]  D. Eckberg.  Point:counterpoint: respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism. , 2008, Journal of applied physiology.

[14]  Berend E. Westerhof,et al.  The arterial Windkessel , 2009, Medical & Biological Engineering & Computing.

[15]  M. Ursino,et al.  Cardiovascular changes in cardiogenic and obstructive shocks: Analysis using a cardiopulmonary simulation model , 2008, 2008 Computers in Cardiology.

[16]  Vera Novak,et al.  Sensitivity Analysis and Model Assessment: Mathematical Models for Arterial Blood Flow and Blood Pressure , 2008, Cardiovascular engineering.

[17]  Christian Putensen,et al.  CHAPTER 23 – Inverse Ratio Ventilation , 2008 .

[18]  Maxwell Lewis Neal,et al.  Subject-specific Model Estimation of Cardiac Output and Blood Volume During Hemorrhage , 2007, Cardiovascular engineering.

[19]  John E. Remmers,et al.  Model based analysis of sleep disordered breathing in congestive heart failure , 2007, Respiratory Physiology & Neurobiology.

[20]  L. Chiari,et al.  A comprehensive simulator of the human respiratory system: Validation with experimental and simulated data , 1997, Annals of Biomedical Engineering.

[21]  M. Ursino,et al.  Cardiovascular response to dynamic aerobic exercise: A methematical model , 2002, Medical and Biological Engineering and Computing.

[22]  R. Mellins,et al.  Computational expressions for blood oxygen and carbon dioxide concentrations , 2006, Annals of Biomedical Engineering.

[23]  Noriaki Ikeda,et al.  A model of overall regulation of body fluids , 2006, Annals of Biomedical Engineering.

[24]  M. Sudhakar,et al.  Carbon dioxide transport , 2005 .

[25]  F. Michard,et al.  Changes in Arterial Pressure during Mechanical Ventilation , 2005, Anesthesiology.

[26]  J. Michael.  Textbook of Medical Physiology , 2005 .

[27]  E. L. Ritman,et al.  Myocardial volume perfused by coronary artery branches — a three-dimensional x-ray CT evaluation in human cadaver hearts , 2005, The International Journal of Cardiac Imaging.

[28]  M. B. Jaffe,et al.  Capnographic waveforms in the mechanically ventilated patient. , 2005, Respiratory care.

[29]  Stanley Heshka,et al.  Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. , 2004, Journal of applied physiology.

[30]  Marc J Poulin,et al.  Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide. , 2004, Journal of applied physiology.

[31]  Johnny T. Ottesen,et al.  A cardiovascular model , 2004 .

[32]  F. Ghorbel,et al.  Cerebral autoregulation and gas exchange studied using a human cardiopulmonary model , 2003, Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439).

[33]  John W. Clark,et al.  Whole-Body Gas Exchange in Human Predicted by a Cardiopulmonary Model , 2003 .

[34]  Mauro Ursino,et al.  A theoretical analysis of the carotid body chemoreceptor response to O2 and CO2 pressure changes , 2002, Respiratory Physiology & Neurobiology.

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

[36]  F. Ghorbel,et al.  A human cardiopulmonary system model applied to the analysis of the Valsalva maneuver. , 2001, American journal of physiology. Heart and circulatory physiology.

[37]  E Magosso,et al.  A mathematical model of CO2 effect on cardiovascular regulation. , 2001, American journal of physiology. Heart and circulatory physiology.

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

[39]  C. Cobelli,et al.  Mathematical Models of Respiratory Mechanics , 2001 .

[40]  G Avanzolini,et al.  An integrated model of the human ventilatory control system: the response to hypercapnia. , 2001, Clinical physiology.

[41]  E. Sasaki,et al.  Pancreatic volume in type 1 und type 2 diabetes mellitus , 2001, Acta Diabetologica.

[42]  S. Sletting,et al.  The volume of the liver in patients correlates to body weight and alcohol consumption. , 2000, Alcohol and alcoholism.

[43]  E Magosso,et al.  Acute cardiovascular response to isocapnic hypoxia. I. A mathematical model. , 2000, American journal of physiology. Heart and circulatory physiology.

[44]  John W. Clark,et al.  ENERGY ANALYSIS OF A NONLINEAR MODEL OF THE NORMAL HUMAN LUNG , 2000 .

[45]  R Stephenson,et al.  A model of the chemoreflex control of breathing in humans: model parameters measurement. , 2000, Respiration physiology.

[46]  Y. A. Mengesha.  Variability of cardiovascular responses to hypercapnia in Man , 2000 .

[47]  三平 将彦.  頭蓋内圧に及ぼすInverse Ratio Ventilationの影響 , 2000 .

[48]  W. Timmons,et al.  Cardiovascular Models and Control , 1999 .

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

[50]  W. Mapleson,et al.  Ventilatory assistance and respiratory muscle activity. 2: Simulation with an adaptive active ("aa" or "a-squared") model lung. , 1998, British journal of anaesthesia.

[51]  Doktor Rerum Naturalium,et al.  A Global Model for the Cardiovascular and Respiratory System , 1998 .

[52]  S Field,et al.  Vessel growth and collapsible pressure-area relationship. , 1997, The American journal of physiology.

[53]  B. Lipworth,et al.  Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. , 1996, Chest.

[54]  P. Sheedy,et al.  Reproducibility of human kidney perfusion and volume determinations with electron beam computed tomography. , 1996, Investigative radiology.

[55]  D. Cunningham,et al.  Nature of the interaction between central and peripheral chemoreceptor drives in human subjects. , 1996, Canadian journal of physiology and pharmacology.

[56]  E. Gruber,et al.  Cardiopulmonary interactions. , 1996, Acta anaesthesiologica Scandinavica. Supplementum.

[57]  G. Cerri,et al.  Sonographic assessment of normal spleen volume , 1995, Clinical anatomy.

[58]  Vincent C. Rideout,et al.  Mathematical and Computer Modeling of Physiological Systems , 1991 .

[59]  T G Coleman,et al.  HUMAN. A comprehensive physiological model. , 1983, The Physiologist.

[60]  John F. Nunn,et al.  Respiratory Physiology—the essentials , 1975 .

[61]  E. d’Angelo,et al.  Continuous recording of pleural surface pressure at various sites. , 1973, Respiration physiology.

[62]  H T Milhorn,et al.  Transient ventilatory response to hypoxia with and without controlled alveolar PCO2. , 1973, Journal of applied physiology.

[63]  J. Greenfield,et al.  Pressure‐Flow Studies in Man: Effect of Respiration on Left Ventricular Stroke Volume , 1973, Circulation.

[64]  H T Milhorn,et al.  Transient ventilatory response to graded hypercapnia in man. , 1972, Journal of applied physiology.

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

[66]  G. Cumming,et al.  A model of time-varying gas exchange in the human lung during a respiratory cycle at rest. , 1971, Scandinavian journal of respiratory diseases. Supplementum.

[67]  Edward D. Crandall,et al.  An analysis of external respiration in man , 1968 .

[68]  G Grimby,et al.  Frequency dependence of flow resistance in patients with obstructive lung disease. , 1968, The Journal of clinical investigation.

[69]  B. Ferris,et al.  PARTITIONING OF RESPIRATORY FLOW RESISTANCE IN MAN. , 1964, Journal of applied physiology.

[70]  F. Grodins.  Integrative Cardiovascular Physiology: A Mathematical Synthesis of Cardiac and Blood Vessel Hemodynamics , 1959, The Quarterly Review of Biology.

[71]  R. W. Jones,et al.  Respiratory responses to CO2 inhalation; a theoretical study of a nonlinear biological regulator. , 1954, Journal of applied physiology.