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. 2003 Jun;11(6):250-258, 259.

Heart rate variability and sympathovagal balance: pharmacological validation

M Bootsma, CA Swenne, MJA Janssen, V Manger Cats, MJ Schalij
PMCID: PMC2499895  PMID: 25696224

Abstract

Rationale

We validated heart rate (HR) and six time and six frequency domain measures of heart rate variability (HRV) as estimators of autonomic outflow in 44 young healthy male subjects. Gold standards for autonomic outflow were the Rosenblueth-Simeone factors m (sympathetic tone) and n (vagal tone), and the sympathovagal balance m·n, determined by two-stage complete autonomic blockade.

Methods

Rank correlations were computed between HR and the HRV measures obtained before autonomic blockade, and m, n and m·n. Also, the maximal mean performances (averaged sensitivity and specificity) for HR and HRV as discriminators between low and high values of m, n or m·n were computed.

Results

The spectral HRV measures showed less good correlations and performances than the time domain HRV measures. Correlations with sympathetic tone were all below 0.31. Respiratory sinus arrhythmia during 15 cycles/min metronome breathing was superior in estimating vagal tone and sympathovagal balance (correlations -0.71/-0.73; both performances 0.82), heart rate scored similarly for assessing the sympathovagal balance (correlation 0.71; performance 0.82).

Conclusions

It does not appear justified to evaluate HR or HRV in terms of sympathetic tone, vagal tone, or sympathovagal balance. HR and HRV are specifically weak in assessing sympathetic tone. Respiratory sinus arrhythmia during 15 cycles/min metronome breathing is superior in assessing vagal tone. Current HRV analysis techniques offer no advantages compared with HR in assessing the sympathovagal balance.

Keywords: atropine, metoprolol, heart rate variability, Rosenblueth-Simeone model, sympathovagal balance

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akselrod S., Gordon D., Madwed J. B., Snidman N. C., Shannon D. C., Cohen R. J. Hemodynamic regulation: investigation by spectral analysis. Am J Physiol. 1985 Oct;249(4 Pt 2):H867–H875. doi: 10.1152/ajpheart.1985.249.4.H867. [DOI] [PubMed] [Google Scholar]
  2. Appel M. L., Berger R. D., Saul J. P., Smith J. M., Cohen R. J. Beat to beat variability in cardiovascular variables: noise or music? J Am Coll Cardiol. 1989 Nov 1;14(5):1139–1148. doi: 10.1016/0735-1097(89)90408-7. [DOI] [PubMed] [Google Scholar]
  3. Berger R. D., Saul J. P., Cohen R. J. Transfer function analysis of autonomic regulation. I. Canine atrial rate response. Am J Physiol. 1989 Jan;256(1 Pt 2):H142–H152. doi: 10.1152/ajpheart.1989.256.1.H142. [DOI] [PubMed] [Google Scholar]
  4. Bernardi L., Keller F., Sanders M., Reddy P. S., Griffith B., Meno F., Pinsky M. R. Respiratory sinus arrhythmia in the denervated human heart. J Appl Physiol (1985) 1989 Oct;67(4):1447–1455. doi: 10.1152/jappl.1989.67.4.1447. [DOI] [PubMed] [Google Scholar]
  5. Bigger J. T., Jr, Fleiss J. L., Steinman R. C., Rolnitzky L. M., Kleiger R. E., Rottman J. N. Correlations among time and frequency domain measures of heart period variability two weeks after acute myocardial infarction. Am J Cardiol. 1992 Apr 1;69(9):891–898. doi: 10.1016/0002-9149(92)90788-z. [DOI] [PubMed] [Google Scholar]
  6. Bootsma M., Swenne C. A., Lenders J. W., Jacobs M. C., Bruschke A. V. Intravenous instrumentation alters the autonomic state in humans. Eur J Appl Physiol Occup Physiol. 1996;73(1-2):113–116. doi: 10.1007/BF00262818. [DOI] [PubMed] [Google Scholar]
  7. Bootsma M., Swenne C. A., Van Bolhuis H. H., Chang P. C., Cats V. M., Bruschke A. V. Heart rate and heart rate variability as indexes of sympathovagal balance. Am J Physiol. 1994 Apr;266(4 Pt 2):H1565–H1571. doi: 10.1152/ajpheart.1994.266.4.H1565. [DOI] [PubMed] [Google Scholar]
  8. Eckberg D. L. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol Respir Environ Exerc Physiol. 1983 Apr;54(4):961–966. doi: 10.1152/jappl.1983.54.4.961. [DOI] [PubMed] [Google Scholar]
  9. Eckberg D. L., Kifle Y. T., Roberts V. L. Phase relationship between normal human respiration and baroreflex responsiveness. J Physiol. 1980 Jul;304:489–502. doi: 10.1113/jphysiol.1980.sp013338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eckberg D. L. Sympathovagal balance: a critical appraisal. Circulation. 1997 Nov 4;96(9):3224–3232. doi: 10.1161/01.cir.96.9.3224. [DOI] [PubMed] [Google Scholar]
  11. Fetsch T., Reinhardt L., Mäkijärvi M., Böcker D., Block M., Borggrefe M., Breithardt G. Heart rate variability in time domain after acute myocardial infarction. Clin Sci (Lond) 1996;91 (Suppl):136–140. doi: 10.1042/cs0910136supp. [DOI] [PubMed] [Google Scholar]
  12. Fouad F. M., Tarazi R. C., Ferrario C. M., Fighaly S., Alicandri C. Assessment of parasympathetic control of heart rate by a noninvasive method. Am J Physiol. 1984 Jun;246(6 Pt 2):H838–H842. doi: 10.1152/ajpheart.1984.246.6.H838. [DOI] [PubMed] [Google Scholar]
  13. Hayano J., Sakakibara Y., Yamada A., Yamada M., Mukai S., Fujinami T., Yokoyama K., Watanabe Y., Takata K. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol. 1991 Jan 15;67(2):199–204. doi: 10.1016/0002-9149(91)90445-q. [DOI] [PubMed] [Google Scholar]
  14. Hayano J., Sakakibara Y., Yamada M., Ohte N., Fujinami T., Yokoyama K., Watanabe Y., Takata K. Decreased magnitude of heart rate spectral components in coronary artery disease. Its relation to angiographic severity. Circulation. 1990 Apr;81(4):1217–1224. doi: 10.1161/01.cir.81.4.1217. [DOI] [PubMed] [Google Scholar]
  15. Hedman A. E., Hartikainen J. E., Tahvanainen K. U., Hakumäki M. O. Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs. Acta Physiol Scand. 1992 Oct;146(2):155–164. doi: 10.1111/j.1748-1716.1992.tb09404.x. [DOI] [PubMed] [Google Scholar]
  16. Huikuri H. V., Seppänen T., Koistinen M. J., Airaksinen J., Ikäheimo M. J., Castellanos A., Myerburg R. J. Abnormalities in beat-to-beat dynamics of heart rate before the spontaneous onset of life-threatening ventricular tachyarrhythmias in patients with prior myocardial infarction. Circulation. 1996 May 15;93(10):1836–1844. doi: 10.1161/01.cir.93.10.1836. [DOI] [PubMed] [Google Scholar]
  17. Jose A. D., Collison D. The normal range and determinants of the intrinsic heart rate in man. Cardiovasc Res. 1970 Apr;4(2):160–167. doi: 10.1093/cvr/4.2.160. [DOI] [PubMed] [Google Scholar]
  18. Jose A. D., Taylor R. R. Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. J Clin Invest. 1969 Nov;48(11):2019–2031. doi: 10.1172/JCI106167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katona P. G., Jih F. Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control. J Appl Physiol. 1975 Nov;39(5):801–805. doi: 10.1152/jappl.1975.39.5.801. [DOI] [PubMed] [Google Scholar]
  20. Katona P. G., Martin P. J., Jih F. Neural control of heart rate: a conciliation of models. IEEE Trans Biomed Eng. 1976 Mar;23(2):164–166. doi: 10.1109/tbme.1976.324579. [DOI] [PubMed] [Google Scholar]
  21. Katona P. G., McLean M., Dighton D. H., Guz A. Sympathetic and parasympathetic cardiac control in athletes and nonathletes at rest. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jun;52(6):1652–1657. doi: 10.1152/jappl.1982.52.6.1652. [DOI] [PubMed] [Google Scholar]
  22. Katona P. G., Poitras J. W., Barnett G. O., Terry B. S. Cardiac vagal efferent activity and heart period in the carotid sinus reflex. Am J Physiol. 1970 Apr;218(4):1030–1037. doi: 10.1152/ajplegacy.1970.218.4.1030. [DOI] [PubMed] [Google Scholar]
  23. Kleiger R. E., Miller J. P., Bigger J. T., Jr, Moss A. J. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987 Feb 1;59(4):256–262. doi: 10.1016/0002-9149(87)90795-8. [DOI] [PubMed] [Google Scholar]
  24. Levy M. N., DeGeest H., Zieske H. Effects of respiratory center activity on the heart. Circ Res. 1966 Jan;18(1):67–78. doi: 10.1161/01.res.18.1.67. [DOI] [PubMed] [Google Scholar]
  25. Lewis S. F., Nylander E., Gad P., Areskog N. H. Non-autonomic component in bradycardia of endurance trained men at rest and during exercise. Acta Physiol Scand. 1980 Jul;109(3):297–305. doi: 10.1111/j.1748-1716.1980.tb06600.x. [DOI] [PubMed] [Google Scholar]
  26. Maciel B. C., Gallo Júnior L., Marin Neto J. A., Lima Filho E. C., Terra Filho J., Manço J. C. Parasympathetic contribution to bradycardia induced by endurance training in man. Cardiovasc Res. 1985 Oct;19(10):642–648. doi: 10.1093/cvr/19.10.642. [DOI] [PubMed] [Google Scholar]
  27. Malliani A., Pagani M., Lombardi F., Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991 Aug;84(2):482–492. doi: 10.1161/01.cir.84.2.482. [DOI] [PubMed] [Google Scholar]
  28. Melcher A. Carotid baroreflex heart rate control during the active and the assisted breathing cycle in man. Acta Physiol Scand. 1980 Feb;108(2):165–171. doi: 10.1111/j.1748-1716.1980.tb06514.x. [DOI] [PubMed] [Google Scholar]
  29. Odemuyiwa O., Malik M., Farrell T., Bashir Y., Poloniecki J., Camm J. Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction. Am J Cardiol. 1991 Aug 15;68(5):434–439. doi: 10.1016/0002-9149(91)90774-f. [DOI] [PubMed] [Google Scholar]
  30. Rautaharju P. M., Blackburn H. W., Warren J. W. The concepts of sensitivity, specificity and accuracy in evaluation of electrocardiographic, vectorcardiographic and polarcardiographic criteria. J Electrocardiol. 1976;9(3):275–281. doi: 10.1016/s0022-0736(76)80057-x. [DOI] [PubMed] [Google Scholar]
  31. Saul J. P., Arai Y., Berger R. D., Lilly L. S., Colucci W. S., Cohen R. J. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol. 1988 Jun 1;61(15):1292–1299. doi: 10.1016/0002-9149(88)91172-1. [DOI] [PubMed] [Google Scholar]
  32. Saul J. P., Berger R. D., Albrecht P., Stein S. P., Chen M. H., Cohen R. J. Transfer function analysis of the circulation: unique insights into cardiovascular regulation. Am J Physiol. 1991 Oct;261(4 Pt 2):H1231–H1245. doi: 10.1152/ajpheart.1991.261.4.H1231. [DOI] [PubMed] [Google Scholar]
  33. Saul J. P., Rea R. F., Eckberg D. L., Berger R. D., Cohen R. J. Heart rate and muscle sympathetic nerve variability during reflex changes of autonomic activity. Am J Physiol. 1990 Mar;258(3 Pt 2):H713–H721. doi: 10.1152/ajpheart.1990.258.3.H713. [DOI] [PubMed] [Google Scholar]
  34. Seals D. R., Suwarno N. O., Joyner M. J., Iber C., Copeland J. G., Dempsey J. A. Respiratory modulation of muscle sympathetic nerve activity in intact and lung denervated humans. Circ Res. 1993 Feb;72(2):440–454. doi: 10.1161/01.res.72.2.440. [DOI] [PubMed] [Google Scholar]
  35. Shykoff B. E., Naqvi S. S., Menon A. S., Slutsky A. S. Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation. J Clin Invest. 1991 May;87(5):1621–1627. doi: 10.1172/JCI115176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Smith M. L., Hudson D. L., Graitzer H. M., Raven P. B. Exercise training bradycardia: the role of autonomic balance. Med Sci Sports Exerc. 1989 Feb;21(1):40–44. doi: 10.1249/00005768-198902000-00008. [DOI] [PubMed] [Google Scholar]
  37. Stefenelli T., Bergler-Klein J., Globits S., Pacher R., Glogar D. Heart rate behaviour at different stages of congestive heart failure. Eur Heart J. 1992 Jul;13(7):902–907. doi: 10.1093/oxfordjournals.eurheartj.a060290. [DOI] [PubMed] [Google Scholar]
  38. Volosin K. J., Brachfeld C., Beauregard L. A., Fabiszewski R., Waxman H. L. Effect of cigarette smoke on sinus node automaticity. Am J Cardiol. 1990 Jan 15;65(3):243–245. doi: 10.1016/0002-9149(90)90093-g. [DOI] [PubMed] [Google Scholar]
  39. Wallin B. G., Esler M., Dorward P., Eisenhofer G., Ferrier C., Westerman R., Jennings G. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol. 1992;453:45–58. doi: 10.1113/jphysiol.1992.sp019217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Warner H. R., Russell R. O., Jr Effect of combined sympathetic and vagal stimulation on heart rate in the dog. Circ Res. 1969 Apr;24(4):567–573. doi: 10.1161/01.res.24.4.567. [DOI] [PubMed] [Google Scholar]
  41. Warzel H., Eckhardt H. U., Hopstock U. Effects of carotid sinus nerve stimulation at different times in the respiratory and cardiac cycles on variability of heart rate and blood pressure of normotensive and renal hypertensive dogs. J Auton Nerv Syst. 1989 Mar;26(2):121–127. doi: 10.1016/0165-1838(89)90160-4. [DOI] [PubMed] [Google Scholar]
  42. deBoer R. W., Karemaker J. M., Strackee J. Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. Am J Physiol. 1987 Sep;253(3 Pt 2):H680–H689. doi: 10.1152/ajpheart.1987.253.3.H680. [DOI] [PubMed] [Google Scholar]
  43. van Ravenswaaij-Arts C. M., Kollée L. A., Hopman J. C., Stoelinga G. B., van Geijn H. P. Heart rate variability. Ann Intern Med. 1993 Mar 15;118(6):436–447. doi: 10.7326/0003-4819-118-6-199303150-00008. [DOI] [PubMed] [Google Scholar]

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