Parametric description of cardiac vagal control

Heart rate variability (HRV) indices that reflect the magnitude of respiratory sinus arrhythmia (RSA) are commonly applied as non-invasive measures of cardiac vagal control. Recently, however, serious doubts have been raised about the accuracy and validity of such assessments. To evaluate these methods, we derived a theoretical model for the dependence of mean heart rate and RSA on gradual vagal blockade by atropine, and compared its predictions to actual experimental results. The experiment involved the injection of nine consecutive intravenous bolus doses of atropine to eight young healthy male subjects. Seven-minute recordings of ECG and respiration were made for each atropine dose. The heart rate (HR) signal was derived from the ECG recording, and mean heart rate and the power of the high frequency peak of HRV (which measures the magnitude of RSA) were computed. The experimental data were fitted to the model's equations, and optimal values were obtained for the model's parameters. A tight agreement is observed between the theoretical fitted curves and the experimental data. The parameters that were computed from fitting the experimental data to the mean heart rate equation display a surprisingly small variance among the different subjects. The parameters that were computed from fitting the experimental data to the RSA equation, and the resulting shape of these fitted curves, explain many of the conflicting results previously published, and provide a new quantitative insight to cardiac vagal activity.

[1]  A R LeBlanc,et al.  Transfer function analysis of vagal control of heart rate during synchronized vagal stimulation. , 1995, The American journal of physiology.

[2]  A Calciati,et al.  Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise? , 1990, Cardiovascular research.

[3]  G. Anrep,et al.  Respiratory Variations of the Heart Rate. I.--The Reflex Mechanism of the Respiratory Arrhythmia , 1936 .

[4]  Y Rudy,et al.  Mathematical model of dependence of heart rate on tissue concentration of acetylcholine. , 1989, The American journal of physiology.

[5]  D. Adam,et al.  Assessment of autonomic function in humans by heart rate spectral analysis. , 1985, The American journal of physiology.

[6]  P G Katona,et al.  Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control. , 1975, Journal of applied physiology.

[7]  Sarit Abramovich-Sivan,et al.  A simulation of the SA node by a phase response curve-based model of a two-dimensional pacemaker cells array , 2000, IEEE Transactions on Biomedical Engineering.

[8]  Pablo Laguna,et al.  Improved heart rate variability signal analysis from the beat occurrence times according to the IPFM model , 2000, IEEE Transactions on Biomedical Engineering.

[9]  R. Cohen,et al.  Hemodynamic regulation: investigation by spectral analysis. , 1985, The American journal of physiology.

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

[11]  R. Tarazi,et al.  Assessment of parasympathetic control of heart rate by a noninvasive method. , 1984, The American journal of physiology.

[12]  Y. Benjamini,et al.  Paradoxical pharmacodynamic effect of atropine on parasympathetic control: A study by spectral analysis of heart rate fluctuations , 1992, Clinical pharmacology and therapeutics.

[13]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .

[14]  Alan V. Oppenheim,et al.  Discrete-Time Signal Pro-cessing , 1989 .

[15]  M. Lew,et al.  Analysis of competitive agonist-antagonist interactions by nonlinear regression. , 1995, Trends in pharmacological sciences.

[16]  J. Saul,et al.  Transfer function analysis of autonomic regulation. I. Canine atrial rate response. , 1989, The American journal of physiology.

[17]  A. Camm,et al.  Components of heart rate variability--what they really mean and what we really measure. , 1993, The American journal of cardiology.

[18]  R. Lyman Ott.,et al.  An introduction to statistical methods and data analysis , 1977 .

[19]  A Calciati,et al.  Determinants of respiratory sinus arrhythmia in the vagotomized rabbit. , 1995, The American journal of physiology.

[20]  P. Grossman,et al.  Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: within- and between-individual relations. , 1993, Psychophysiology.

[21]  Modulation of the dose-dependent effects of atropine by low-dose pyridostigmine: Quantification by spectral analysis of heart rate fluctuations in healthy human beings , 1991, Pharmacology Biochemistry and Behavior.

[22]  D L Eckberg,et al.  Muscarinic cholinergic receptors modulate vagal cardiac responses in man. , 1983, Journal of the autonomic nervous system.

[23]  C L Feldman,et al.  Determinants of heart rate variability. , 1996, Journal of the American College of Cardiology.

[24]  P G Katona,et al.  Cardiac vagal efferent activity and heart period in the carotid sinus reflex. , 1970, The American journal of physiology.

[25]  G H Pollack,et al.  Threshold effects of acetylcholine on primary pacemaker cells of the rabbit sino-atrial node , 1985, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[26]  F Lombardi,et al.  Role of the Input/Output Relation of Sinoatrial Myocytes in Cholinergic Modulation of Heart Rate Variability , 2000, Journal of cardiovascular electrophysiology.

[27]  Claire Médigue,et al.  Relationship between pulse interval and respiratory sinus arrhythmia: a time- and frequency-domain analysis of the effects of atropine , 2001, Pflügers Archiv.

[28]  Michele A. Parker,et al.  Relationship of Heart Rate Variability to Parasympathetic Effect , 2001, Circulation.

[29]  J. Hayano,et al.  Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. , 1991, The American journal of cardiology.

[30]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[31]  A. Kadish,et al.  Effect of Graded Increases in Parasympathetic Tone on Heart Rate Variability , 1996, Journal of cardiovascular electrophysiology.

[32]  M. Kollai,et al.  Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man. , 1990, The Journal of physiology.

[33]  A. Wellstein,et al.  Complex dose-response curves of atropine in man explained by different functions of M1- and M2-cholinoceptors , 1988, Naunyn-Schmiedeberg's Archives of Pharmacology.

[34]  M. Sugimachi,et al.  Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[35]  Solange Akselrod,et al.  Functional restitution of cardiac control in heart transplant patients. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[36]  J. Hartikainen,et al.  The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic 'tone'. , 1995, Acta physiologica Scandinavica.

[37]  H. Nagaraja,et al.  Heart rate variability: origins, methods, and interpretive caveats. , 1997, Psychophysiology.

[38]  Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: A possible bioequivalent probe , 1991, Neuroscience & Biobehavioral Reviews.

[39]  R. Cohen,et al.  An Efficient Algorithm for Spectral Analysis of Heart Rate Variability , 1986, IEEE Transactions on Biomedical Engineering.

[40]  Solange Akselrod,et al.  Do the high-frequency indexes of HRV provide a faithful assessment of cardiac vagal tone? A critical theoretical evaluation , 2003, IEEE Transactions on Biomedical Engineering.

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

[42]  A. Kadish,et al.  Dissociation of heart rate variability from parasympathetic tone. , 1994, The American journal of physiology.

[43]  D L Eckberg,et al.  Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans. , 2001, American journal of physiology. Heart and circulatory physiology.

[44]  J. Hartikainen,et al.  Effect of sympathetic modulation and sympatho-vagal interaction on heart rate variability in anaesthetized dogs. , 1995, Acta physiologica Scandinavica.

[45]  J. Saul,et al.  Transfer function analysis of the circulation: unique insights into cardiovascular regulation. , 1991, The American journal of physiology.

[46]  Solange Akselrod,et al.  Wavelet analysis of instantaneous heart rate: a study of autonomic control during thrombolysis. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.