Sympathetic — Parasympathetic Interaction and Sudden Death

  • E. Vanoli
  • Peter J. Schwartz


The effects of the autonomic nervous system on malignant arrhythmias, particularly in the setting of ischemic heart disease, have been widely investigated and described. Specifically, it has been shown that while sympathetic hyperactivity is arrhythmogenic, an increased vagai activity often exerts a beneficial effect. New insights on the relationship between autonomie activity and sudden cardiac death have been obtained in conscious dogs in which a healed myocardial infarction, acute myocardial ischemia, and exercise are combined. In this chronic animal model it was shown that myocardial infarction reduces baroreflex sensitivity and heart rate variability (markers of vagai reflex and tonic activity to the heart) and that a depressed baroreflex sensitivity or a reduced heart rate variability after myocardial infarction indicate an increased risk for ventricular fibrillation. The validity of these experimental observations was confirmed in clinical studies in patients with a myocardial infarction. The protective effect of vagai activity was further confirmed in two experimental studies in which muscarinic stimulation, both electrically and pharmacologically induced, was able to prevent ventricular fibrillation during acute myocardial ischemia. These observations have led to new research directions. At the experimental level, the effect of Gi proteins activity blockade by pertussis toxin on the cardiac response to vagai activation is currently evaluated in conscious dogs. At the clinical level, the prognostic value after myocardial infarction of baroreflex sensitivity and of heart rate variability will be tested in a large, multicenter, prospective study.


Heart Rate Variability Sudden Death Sudden Cardiac Death Ventricular Fibrillation Vagal Stimulation 
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  1. 1.
    Berger RD, Akselrod S, Gordon D, Cohen RJ (1986) An efficient algorithm for spectral analysis of heart rate variability. IEEE Trans Biomed Eng 9, 900–904CrossRefGoogle Scholar
  2. 2.
    Bigger JT Jr, Kleiger RE, Fleiss JL, Rolnitzky LM, Steinman RC, Miller JP and The Multicenter Post-Infarction Research Group (1988) Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol 61, 208–215PubMedCrossRefGoogle Scholar
  3. 3.
    Bigger JT Jr., La Rovere MT, Steinman RC, Fleiss JL, Rottman JN, Rolnitzky LM, Schwartz PJ (1989) Comparison of baroreflex sensitivity and heart period variability after myocardial infarction. J Am Coll Cardiol 14, 1511–1518PubMedCrossRefGoogle Scholar
  4. 4.
    Billman GE, Schwartz PJ, Stone HL (1982) Baroreceptor reflex control of heart rate: A predictor of sudden cardiac death. Circulation 66, 874–880PubMedCrossRefGoogle Scholar
  5. 5.
    Billman GE, Schwartz PJ, Stone HL (1984) The effects of daily exercise on susceptibility to sudden cardiac death. Circulation 69, 1182–1189PubMedCrossRefGoogle Scholar
  6. 6.
    Billman GE, Schwartz PJ, Gagnol JP, Stone HL (1985) The cardiac response to submaximal exercise in dogs susceptible to sudden cardiac death. J Appl Physiol 59, 890–897PubMedGoogle Scholar
  7. 7.
    Brown AM, Birnbaumer L (1988) Direct G protein gating of ion channels. Am J Physiol 254:H401–H410PubMedGoogle Scholar
  8. 8.
    Cerati D, Schwartz PJ (1989) Vagai reflexes and survival during acute myocardial ischemia in cats. Circulation 80(Suppl II):522 (abstr.)Google Scholar
  9. 9.
    Cohen J (1969) Statistical power analysis for behavioral sciences. New York, Academic Press 89Google Scholar
  10. 10.
    Corr PB, Yamada KA, Witkowski FX (1986) Mechanisms controlling cardiac autonomic function and their relation to arrhythmogenesis. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE (Eds.) The Heart and Cardiovascular System. Vol. II, Raven Press, New York, pp 1343–1403Google Scholar
  11. 11.
    De Ferrari GM, Vanoli E, Stramba-Badiale M, Foreman RD, Schwartz PJ (1987) Vagai stimulation and sudden death in conscious dogs with a healed myocardial infarction. Circulation 76(suppl IV): 107 (abstr.)Google Scholar
  12. 12.
    De Ferrari GM, Vanoli E, Tommasini G, Grossoni M, Uckmar G, Patrono C, Schwartz PJ (1989) Antiarrhythmic effect of muscarinic agonists during acute myocardial ischemia. Circulation 80(Suppl IV):202 (abstr.)Google Scholar
  13. 13.
    Eckberg DL (1983) Human sinus arrhythmia as an index of vagai cardiac outflow. J Appl Physiol 54, 961–966PubMedGoogle Scholar
  14. 14.
    Ewing DJ, Neilson JMM, Travis P (1984) New method for assessing cardiac parasympathetic activity using 24-hour electrocardiograms. Br Heart J 52, 396–402PubMedCrossRefGoogle Scholar
  15. 15.
    Fleming JW, Watanabe AM (1986) Biochemical mechanisms of parasympathetic regulation of cardiac function. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE (Eds.) The Heart and Cardiovascular System, Raven Press, New York, pp 1679–1688Google Scholar
  16. 16.
    Fleming JW, Hodges TD, Watanabe AM (1988) Pertussis toxin-treated dog: A whole animal model of impaired inhibitory regulation of adenylate cyclase. Circ Res 62, 992–1000PubMedCrossRefGoogle Scholar
  17. 17.
    Gilman AG (1984) G proteins and dual control of adenylate cyclase. Cell 36, 577–579PubMedCrossRefGoogle Scholar
  18. 18.
    Gnecchi Ruscone T, Lombardi F, Malfatto G, Malliani A (1987) Attenuation of baroreceptive mechanisms by cardiovascular sympathetic afferent fibers. Am J Physiol 253:H787–H791PubMedGoogle Scholar
  19. 19.
    Hull SS, Vanoli E, Adamson PB, Green FJ, De Ferrari GM, Foreman RD, Schwartz PJ, Watanabe AM (1989) Pertussis toxin alters vagai control of heart rate in conscious dogs. Circulation 80(Suppl II): 12 (abstr.)Google Scholar
  20. 20.
    Hull SS, Evans A, Vanoli E, Adamson PB, Albert DE, Foreman RD, Stramba-Badiale M, Schwartz PJ (1990) Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. J Am Coll Cardiol 16, 978–985PubMedCrossRefGoogle Scholar
  21. 21.
    Katona PG, Jih F (1975) Respiratory sinus arrhythmia: Noninvasive measure of parasympathetic cardiac control. J Appl Physiol 39, 801–805PubMedGoogle Scholar
  22. 22.
    Kay SM, Marple SL (1981) Spectrum analysis: A modern perspective. Proc IEEE 69, 1380–1419CrossRefGoogle Scholar
  23. 23.
    Kent KM, Smith ER, Redwood DR, Epstein SE (1973) Electrical stability of acutely ischemic myocardium: Influence of heart rate and vagai stimulation. Circulation 47, 291–298PubMedCrossRefGoogle Scholar
  24. 24.
    Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, and The Multicenter Post-Infarction Research Group (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59, 256–262PubMedCrossRefGoogle Scholar
  25. 25.
    Kunze DL (1972) Reflex discharge patterns of cardiac vagai efferent fibres. J Physiol 222, 1–15PubMedGoogle Scholar
  26. 26.
    La Rovere MT, Specchia G, Mortara A, Schwartz PJ (1988) Baroreflex sensitivity, clinical correlates and cardiovascular mortality among patients with a first myocardial infarction: A prospective study. Circulation 78, 816–824PubMedCrossRefGoogle Scholar
  27. 27.
    Lombardi F, Sandrone G, Pernpruner S, Sala R, Garimoldi M, Cerutti S, Baselli G, Pagani M, Malliani A (1987) Heart rate variability as an index of sympathovagal interaction after acute myocardial infarction. Am J Cardiol 60, 1239–1245PubMedCrossRefGoogle Scholar
  28. 28.
    Lown B (1979) Sudden cardiac death: The major challenge confronting contemporary cardiology. Am J Cardiol 43, 313–320PubMedCrossRefGoogle Scholar
  29. 29.
    Mancia G, Mark AL (1983) Arterial baroreflexes in humans. In: Shephard JL, Abboud FM (Eds.) Handbook of Physiology: The Cardiovascular System, Vol. III. Bethesda, Md, Am Physiol Soc, pp 755–793Google Scholar
  30. 30.
    Myers GA, Martin GJ, Magid NM, Barnett PS, Schaad JW, Weiss JS, Lesch M, Singer DH (1986) Power spectral analysis of heart rate variability in sudden cardiac death: Comparison to other methods. IEEE Trans Biomed Eng 33, 1149–1156PubMedCrossRefGoogle Scholar
  31. 31.
    Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell’Orto S, Piccaluga E, Turiel M, Basselli G, Cerutti S, Malliani A (1986) Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 59, 178–193PubMedCrossRefGoogle Scholar
  32. 32.
    Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H (1985) Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 248:H151–H153PubMedGoogle Scholar
  33. 33.
    Priori SG, Zuanetti G, Schwartz PJ (1988) Ventricular fibrillation induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity: Effect of nifedipine. Am Heart J 116, 37–43PubMedCrossRefGoogle Scholar
  34. 34.
    Rich MW, Saini JS, Kleiger RE, Carney RM, teVelde A, Freedland KE (1988) Correlation of heart rate variability with clinical and angiographic variables and late mortality after coronary angiography. Am J Cardiol 62, 714–717PubMedCrossRefGoogle Scholar
  35. 35.
    Rothschild M, Rothschild A, Pfeifer M (1988) Temporary decrease in cardiac parasympathetic tone after acute myocardial infarction. Am J Cardiol 62, 637–639PubMedCrossRefGoogle Scholar
  36. 36.
    Scheuer J, Tipton CM (1979) Cardiovascular adaptation to physical training. Ann Rev Physiol 39, 221–251CrossRefGoogle Scholar
  37. 37.
    Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM (1973) A cardiocardiac sympatho-vagal reflex in the cat. Circ Res 32, 215–220PubMedCrossRefGoogle Scholar
  38. 38.
    Schwartz PJ, Stone HL, Brown AM (1976) Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion. Am Heart J 92, 589–599PubMedCrossRefGoogle Scholar
  39. 39.
    Schwartz PJ, Brown AM, Malliani A, Zanchetti A (Eds.) (1978) Neural Mechanisms in Cardiac Arrhythmias. Raven Press, New YorkGoogle Scholar
  40. 40.
    Schwartz PJ, Vanoli E (1981) Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs. J Cardiovasc Pharmacol 3, 1251–1259PubMedCrossRefGoogle Scholar
  41. 41.
    Schwartz PJ, Billman GE, Stone HL (1984) Autonomie mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with a healed myocardial infarction. An experimental preparation for sudden cardiac death. Circulation 69, 780–790CrossRefGoogle Scholar
  42. 42.
    Schwartz PJ, Stone HL (1985) The analysis and modulation of autonomie reflexes in the prediction and prevention of sudden death. In: Zipes DP, Jalife J (Eds.) Cardiac Arrhythmias: Mechanisms and Management, Grune and Stratton, New York, pp 165–176Google Scholar
  43. 43.
    Schwartz PJ, Vanoli E, Zaza A, Zuanetti G (1985) The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity. Am Heart J 109, 937–948PubMedCrossRefGoogle Scholar
  44. 44.
    Schwartz PJ, Priori SG, Vanoli E, Zaza A, Zuanetti G (1986) Efficacy of diltiazem in two experimental feline models of sudden cardiac death. J Am Coll Cardiol 8, 661–668PubMedCrossRefGoogle Scholar
  45. 45.
    Schwartz PJ, Stramba-Badiale M (1988) Parasympathetic nervous system and cardiac arrhythmias. In: Kulbertus HE, Frank G (Eds.), Neurocardiology, Futura Publishing Co., Mount Kisco, NY, pp 179–200Google Scholar
  46. 46.
    Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD (1988) Autonomie mechanisms and sudden death. New insight from the analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 78, 969–973PubMedCrossRefGoogle Scholar
  47. 47.
    Schwartz PJ, Zaza A, Pala M, Locati E, Beria G, Zanchetti A (1988) Baroreflex sensitivity and its evolution during the first year after a myocardial infarction. J Am Coll Cardiol 12, 629–636PubMedCrossRefGoogle Scholar
  48. 48.
    Schwartz PJ, Priori SG (1990) Sympathetic nervous system and sudden death. In: Zipes DP, Jalife J (Eds.) Cardiac Electrophysiology. From Cell to Bedside, WB Saunders Co, Philadelphia, (In press)Google Scholar
  49. 49.
    Singer DH, Martin GJ, Magid N, Weiss JS, Schaad JW, Kehoe R, Zheutlin T, Fintel DJ, Hsieh AM, Lesch M (1988) Low heart rate variability and sudden cardiac death. J Electrocardiol Suppl: S46-S65Google Scholar
  50. 50.
    Smyth HS, Sleight P, Pickering GW (1969) Reflex regulation of arterial pressure during sleep in man. Circ Res 24, 109–121PubMedCrossRefGoogle Scholar
  51. 51.
    Stone HL (1977) Cardiac function and exercise training in conscious dogs. J Appl Physiol 42, 824–832PubMedGoogle Scholar
  52. 52.
    Stramba-Badiale M, De Ferrari GM, Vanoli E, Billman GE, Hull SS, Foreman RD, Schwartz PJ (1988) Myocardial ischemia and ventricular fibrillation in conscious dogs. Atropine and the role of vagai reflex. Fed Proc 47:A327 (abstr.)Google Scholar
  53. 53.
    Verrier RL (1980) Neural factors and ventricular electrical instability. In: Kulbertus HE, Wellens HJJ (Eds.) Sudden Death, Martinus Nijhoff, The Hague, pp 137–155CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • E. Vanoli
    • 1
  • Peter J. Schwartz
    • 1
  1. 1.Unita’ di Studio delle Aritmie, Centro di Fisiologia Clinica e Ipertensione, Istituto di Clinica Medica IIUniversita’ degli Studi di MilanoMilanItaly

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