Modeling baroreflex regulation of heart rate during orthostatic stress.

During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing.

[1]  H. Rusinek,et al.  Cerebral cortical and white matter reactivity to carbon dioxide. , 1989, Stroke.

[2]  F. Abboud,et al.  Structural versus functional modulation of the arterial baroreflex. , 1995, Hypertension.

[3]  Chiyoshi Yoshimoto,et al.  The Optimal Cardiovascular Regulation of the Arterial Blood Pressure , 1982 .

[4]  Joyce Evans,et al.  Influence of cardiac innervation on intrinsic heart rate in dogs. , 1990, The American journal of physiology.

[5]  R J Cohen,et al.  Heart rate response to hemorrhage-induced 0.05-Hz oscillations in arterial pressure in conscious dogs. , 1991, The American journal of physiology.

[6]  J K Kimani,et al.  Electron microscopic structure and innervation of the carotid baroreceptor region in the rock hyrax (Procavia capensis) , 1992, Journal of morphology.

[7]  A. J. Dunning,et al.  Mechanisms of initial heart rate response to postural change. , 1982, The American journal of physiology.

[8]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[9]  R Peto,et al.  Effect of Age and High Blood Pressure on Barorefiex Sensitivity in Man , 1971, Circulation research.

[10]  H. Warner,et al.  A Mathematical Model of Heart Rate Control by Sympathetic and Vagus Efferent Information , 1962, Journal of applied physiology.

[11]  G. N. Franz,et al.  NONLINEAR RATE SENSITIVITY OF THE CAROTID SINUS REFLEX AS A CONSEQUENCE OF STATIC AND DYNAMIC NONLINEARITIES IN BARORECEPTOR BEHAVIOR * , 1969, Annals of the New York Academy of Sciences.

[12]  F. Abboud,et al.  Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview. , 1994, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[13]  F. Abboud,et al.  Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure. , 1992, The American journal of physiology.

[14]  G. Pickering,et al.  Reflex Regulation of Arterial Pressure during Sleep in Man: A Quantitative Method of Assessing Baroreflex Sensitivity , 1969, Circulation research.

[15]  K. Monahan,et al.  The Vestibulosympathetic Reflex In Humans: Neural Interactions Between Cardiovascular Reflexes , 2002, Clinical and Experimental Pharmacology and Physiology.

[16]  J. Taylor,et al.  Quantification of Mechanical and Neural Components of Vagal Baroreflex in Humans , 2001, Hypertension.

[17]  E. Noldus,et al.  Optimal control aspects of left ventricular ejection dynamics. , 1976, Journal of theoretical biology.

[18]  L. Lipsitz,et al.  Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. , 2000, Stroke.

[19]  L. Ingber,et al.  Statistical Mechanics of Financial Markets: Exponential Modifications to Black-Scholes , 2000 .

[20]  R. Shephard,et al.  Autonomic Regulation of the Circulation During Exercise and Heat Exposure , 1998, Sports medicine.

[21]  D. Harrison,et al.  Sinus node function in the denervated human heart. Effect of digitalis. , 1975, British heart journal.

[22]  P. Reddy,et al.  Respiratory sinus arrhythmia in the denervated human heart. , 1989, Journal of applied physiology.

[23]  Robert C. Gorman,et al.  Baroreceptor responses derived from a fundamental concept , 2006, Annals of Biomedical Engineering.

[24]  Sarah E. Bridges,et al.  Mental stress response, arterial stiffness, and baroreflex sensitivity in healthy aging. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[25]  A. C. Young,et al.  Servoanalysis of Carotid Sinus Reflex Effects on Peripheral Resistance , 1963, Circulation research.

[26]  J. Kampine,et al.  Firing characteristics of single-fiber carotid sinus baroreceptors. , 1990, Circulation research.

[27]  R. Russell,et al.  Effect of Combined Sympathetic and Vagal Stimulation on Heart Rate in the Dog , 1969, Circulation research.

[28]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[29]  Y. Sugiyama,et al.  Delayed and diminished pressor response to muscle sympathetic nerve activity in the elderly. , 1996, Journal of applied physiology.

[30]  F Kappel,et al.  A mathematical model for fundamental regulation processes in the cardiovascular system , 1993, Journal of mathematical biology.

[31]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

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

[33]  J. Uther,et al.  ‘Steady‐state’ properties of the baroreceptor‐heart rate reflex in essential hypertension in man , 1974, Clinical and experimental pharmacology & physiology.

[34]  K. Monahan,et al.  Aging Attenuates the Vestibulosympathetic Reflex in Humans , 2002, Circulation.

[35]  A. J. Honour,et al.  Diminished Baroreflex Sensitivity in High Blood Pressure , 1969, Circulation.

[36]  Detlev W. Bronk,et al.  THE RESPONSE TO STEADY PRESSURES OF SINGLE END ORGANS IN THE ISOLATED CAROTID SINUS , 1934 .

[37]  J. Ottesen Modelling of the baroreflex-feedback mechanism with time-delay , 1997, Journal of mathematical biology.

[38]  Theodore Raphan,et al.  Electrical activation of the human vestibulo-sympathetic reflex , 2006, Experimental Brain Research.

[39]  S M Davis,et al.  Cerebral blood flow and cerebrovascular CO2 reactivity in stroke‐age normal controls , 1983, Neurology.

[40]  B. J. Yates,et al.  Responses of vestibular nucleus neurons to tilt following chronic bilateral removal of vestibular inputs , 2000, Experimental Brain Research.

[41]  G. N. Franz,et al.  Small signal characteristics of carotid sinus baroreceptors of rabbits. , 1971, Journal of applied physiology.

[42]  D L Eckberg,et al.  Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans. , 1988, Acta physiologica Scandinavica.

[43]  Johnny T. Ottesen,et al.  Modelling the dynamical baroreflex-feedback control , 2000 .

[44]  S. Landgren,et al.  On the excitation mechanism of the carotid baroceptors. , 1952, Acta physiologica Scandinavica.

[45]  M. Gizzi,et al.  Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans. , 2002, Experimental brain research.

[46]  M. N. Levy,et al.  Autonomic control of cardiac pacemaker activity and atrioventricular transmission. , 1969, Journal of applied physiology.

[47]  Carl Tim Kelley,et al.  Iterative methods for optimization , 1999, Frontiers in applied mathematics.

[48]  H. Warner,et al.  The Frequency‐Dependent Nature of Blood Pressure Regulation by the Carotid Sinus Studied with an Electric Analog , 1958, Circulation research.

[49]  H. Tran,et al.  Blood pressure and blood flow variation during postural change from sitting to standing: model development and validation. , 2005, Journal of applied physiology.