Pathophysiology of Neurally Mediated Syncope: Peripheral and Central Mechanisms

  • D. G. Benditt
  • K. G. Lurie
  • S. W. Adler
Conference paper


The neurally mediated syncopal syndromes (especially the “common” or vasovagal faint) have long been recognized as being among the most frequent causes of syncope in humans (Table 1; 1–7). Nonetheless, it is only recently (as the availability of tilt-table testing has increased physician awareness) that the pathophysiology and treatment of these syndromes have become the subject of widespread clinical interest (8–11).


Carotid Sinus Nucleus Tractus Solitarius Lower Body Negative Pressure Afferent Signal Vasovagal Syncope 
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  1. 1.
    Lewis T (1932) Vasovagal syncope and the carotid sinus mechanism. With comments on Gower’s and Nothnagel’s syndrome. Br Med J 1: 873–876PubMedCrossRefGoogle Scholar
  2. 2.
    Ross RT (1988) Syncope. ( 1936 ) Saunders, LondonGoogle Scholar
  3. 3.
    Stults BM, Gandolfi RJ (1936) Diagnostic evaluation of syncope. West Med J 144: 234–236Google Scholar
  4. 4.
    Wayne HH (1961) Syncope: physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 30: 418–438PubMedCrossRefGoogle Scholar
  5. 5.
    Ruetz PP, Johnson SA, Callahan R, Meade RC, Smith JJ (1967) Fainting: a review of its mechanisms and a study in blood donors. Medicine (Baltimore) 46: 363–384CrossRefGoogle Scholar
  6. 6.
    Savage DD, Corwin L, McGee DL, Kannell WB, Wolf PA (1985) Epidemiologic features of isolated syncope: the Fram-ingham Study. Stroke 16: 626–629PubMedCrossRefGoogle Scholar
  7. 7.
    Kudenchuk PJ, McAnulty JH (1985) Syncope: evaluation and treatment. Mod Cone Cardiovasc Dis 54: 25–29Google Scholar
  8. 8.
    Almquist A, Goldenberg IF, Milstein S, Chen M-Y, Chen X, Hansen R, Gornick CC, Benditt DG (1989) Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. New Engl J Med 320: 346–351PubMedCrossRefGoogle Scholar
  9. 9.
    Abboud FM (1989) Ventricular syncope. Is the heart a sensory organ? (editorial). New Engl J Med 320: 390–392PubMedCrossRefGoogle Scholar
  10. 10.
    Chen M-Y, Goldenberg IF, Milstein S. Buetikofer J, Almquist A, Lesser J, Benditt DG (1989) Cardiac electrophysiologic and hemodynamic correlates of neurally-mediated syncope. Am J Cardiol 63: 66–72PubMedCrossRefGoogle Scholar
  11. 11.
    Benditt DG, Sakaguchi S, Schultz JJ, Remole S, Adler S, Lurie KG (1993) Syncope. Diagnostic considerations and the role of tilt table testing. Cardiol Rev 1: 146–156CrossRefGoogle Scholar
  12. 12.
    Weiss S, Baker JP (1933) The carotid sinus reflex in health and disease. Its role in the causation of fainting and convulsions. Medicine 12: 297–354CrossRefGoogle Scholar
  13. 13.
    Thomas JE (1969) Hyperactive carotid sinus reflex and carotid sinus syncope. Mayo Clin Proc 44: 127–139PubMedGoogle Scholar
  14. 14.
    Almquist A, Gornick CC, Benson DW Jr, Dunnigan A, Benditt DG (1985) Carotid sinus hypersensitivity: evaluation of the vasodepressor component. Circulation 67: 927–936CrossRefGoogle Scholar
  15. 17.
    Scherrer U, Vissing S, Morgan BJ, Hanson P, Victor RG (1990) Vasovagal syncope after infusion of a vasodilator in a heart-transplant recipient. New Engl J Med 322: 602–604PubMedCrossRefGoogle Scholar
  16. 18.
    van Lieshout JJ, Wieling W, Karemaker JM, Eckberg DL (1991) The vasovagal response. Clin Sei 81: 575–586Google Scholar
  17. 19.
    Abboud F (1993) Neurocardiogenic syncope. N Engl J Med 328: 1117–1120PubMedCrossRefGoogle Scholar
  18. 20.
    Rea R, Thames MD (1993) Neural control mechanisms and vasovagal syncope. J Cardiovasc Electrophysiol 4: 587–595PubMedCrossRefGoogle Scholar
  19. 21.
    Kosinski D, Grubb B, Temesy-Armos P (1995) Pathophysiological aspects of neurocardiogenic syncope: current concepts and new perspectives. PACE 18: 716–724PubMedCrossRefGoogle Scholar
  20. 22.
    Pelletier CL, Shepherd JT (1973) Circulatory reflexes from mechanoreceptors in the cardio-aortic area. Circ Res 33: 131–138PubMedGoogle Scholar
  21. 23.
    Donald DE, Shepherd JT (1978) Reflexes from the heart and lungs: physiological curiosities or important regulatory mechanisms. Cardiovasc Res 12: 449–469CrossRefGoogle Scholar
  22. 24.
    Abboud FM, Thames MD (1983) Interaction of cardiovascular reflexes in circulatory control. In: Shepherd JT, Abbond FM (eds) Peripheral circulation and organ blood flow. American Physiological Society, Bethesda, PA 675–753 (Handbook of physiology, section 2; The Cardiovascular System)Google Scholar
  23. 25.
    Benarroch EE (1993) The central autonomic network. Functional organization, dysfunction, and perspective. Mayo Clin Proc 68: 988–1001PubMedGoogle Scholar
  24. 26.
    Simone F (1990) Vegetative nervous system and syncopes. Funct Neurol 5; 187–192PubMedGoogle Scholar
  25. 27.
    Beiser GD, Zelis R, Epstein SE, Mason DT, Braunwald E (1970) The role of skin and muscle resistance vessels in reflexes mediated by the baroreceptor system. J Clin Invest 49: 225–231PubMedCrossRefGoogle Scholar
  26. 28.
    Wallin BG, Sundlof G (1982) Sympathetic outflow in muscles during vasovagal syncope. J Autonom Nerv Syst 6: 287–291CrossRefGoogle Scholar
  27. 29.
    Goldstein DS, Spanarkel M, Pitterman A, Toltzis R, Gratz E, Epstein S, Keiser HR (1982) Circulatory control mechanisms in vasodepressor syncope. Am Heart J 104: 1071–1075PubMedCrossRefGoogle Scholar
  28. 30.
    Ziegler MG, Echon C, Wilner KD, Specho P, Lake CR Mc- Cutchen JA (1986) Sympathetic nervous withdrawal in the vasodepressor (vasovagal) reaction. J Autonom Nerv Syst 17: 273–278CrossRefGoogle Scholar
  29. 31.
    Muscholl E (1980) Peripheral muscarinic control of norepinephrine release in the cardiovascular system. Am J Physiol 239: H713–720PubMedGoogle Scholar
  30. 32.
    Levy MN (1984) Cardiac sympathetic-parasympathetic interactions. Fed Proc 43: 2598–2602PubMedGoogle Scholar
  31. 33.
    Potter EK (1985) Prolonged non-adrenergic inhibition of cardiac vagal action by sympathetic stimulation: neuromodulation by neuropeptide-Y? Neurosci Lett 54: 117–121PubMedCrossRefGoogle Scholar
  32. 34.
    Potter EK (1987) Presynaptic inhibition of cardiac vagal postganglionic nerves by neuropeptide-Y. Neurosci Lett 83: 101–106PubMedCrossRefGoogle Scholar
  33. 35.
    Revington ML, McCloskey DI (1990) Sympathetic-parasympathetic interactions at the heart, possibly involving neuropeptide Y, in anaesthetized dogs. J Physiol (Lond) 428: 359–370Google Scholar
  34. 36.
    Perry JC, Garson A Jr (1991) The child with recurrent syncope: autonomic function testing and beta-adrenergic hypersensitivity. J Am Coll Cardiol 17: 1168–1171PubMedCrossRefGoogle Scholar
  35. 37.
    Mancia G, Donald DE (1975) Demonstration that atria, ventricles, and lung each are responsible for a tonic inhibition of the vasomotor center in the dog. Circ Res 36: 310–318PubMedGoogle Scholar
  36. 38.
    Share L (1976) Role of cardiovascular receptors in the control of ADH release. Cardiology 61 [Supp 1]: 51–64PubMedCrossRefGoogle Scholar
  37. 39.
    Jarecki M, Thoren PN, Donald DE (1978) Release of renin by the carotid baroreflex in anesthetized dogs: role of cardiopulmonary vagal afferents and renal arterial pressure. Circ Res 42: 614–619PubMedGoogle Scholar
  38. 40.
    Schrier RW, Bichet DG (1981) Osmotic and nonosmotic control of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders. J Lab Clin Med 98: 1–15PubMedGoogle Scholar
  39. 41.
    Thoren P (1979) Role of cardiac vagal C-fibres in cardiovascular control. Rev Physiol Biochem Pharmacol 86: 1–94PubMedCrossRefGoogle Scholar
  40. 42.
    Rowell LB (1986) Human circulation. Regulation during physical stress. Oxford University Press, New YorkGoogle Scholar
  41. 43.
    Barcroft H, Edholm OG, McMichael J, Sharpey-Shafer EP (1944) Posthaemorrhagic fainting. Lancet 1: 489–491CrossRefGoogle Scholar
  42. 44.
    Barcroft H, Edholm OG (1945) On the vasodilatation in human skeletal muscle during posthemorrhagic fainting. J Physiol (Lond) 104: 161–175Google Scholar
  43. 45.
    Oberg B, White S (1970) The role of vagal cardiac nerves and arterial baroreceptors in the circulatory adjustments to hemorrhage in the cat. Acta Physiol Scand 80: 395–403PubMedCrossRefGoogle Scholar
  44. 46.
    Secher NH, Sander-Jensen K, Werner C, Warberg J, Bie P (1984) Bradycardia, a severe but reversible hypovolemic shock in man. Circ Shock 14: 267–274PubMedGoogle Scholar
  45. 47.
    Vingerhoets AJJM (1984) Biochemical changes in two subjects succumbing to syncope. Psychosom Med 46: 95–103PubMedGoogle Scholar
  46. 48.
    Schlesinger Z (1973) Life-threatening “vagal reaction” to physical fitness test. JAMA 226: 1119PubMedCrossRefGoogle Scholar
  47. 49.
    Chosy JJ, Graham DT (1965) Catecholamines in vasovagal fainting. J Psychosom Res 9: 189–194PubMedCrossRefGoogle Scholar
  48. 50.
    Fitzpatrick A, Williams T, Jeffrey C, Lightman S, Sutton R (1990) Pathogenic role for arginine vasopressin (AVP) and catecholamines (EP and NEP) in vasovagal syncope ( Abstract ). J Am Coll Cardiol 15: 98CrossRefGoogle Scholar
  49. 51.
    Sander-Jensen K, Secher NH, Astrup A, Christensen NJ, Giese J, Schwartz TW, Warberg J, Bie P (1986) Hypotension induced by passive head-up tilt: endocrine and circulatory mechanisms. Am J Physiol 251: R742 - R748PubMedGoogle Scholar
  50. 52.
    Abi-Samra F, Maloney JD, Fouad-Tarazi FM, Castle L (1988) The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin. PACE 11: 1202–1214PubMedCrossRefGoogle Scholar
  51. 54.
    Fitzpatrick AP, Theodorakis G, Vardas P, Sutton R (1991) Methodology of head-up tilt testing in patients with unexplained syncope. J Am Coll Cardiol 17: 125–130PubMedCrossRefGoogle Scholar
  52. 55.
    Raviele A, Gasparini G, Di Pede F, Delise P, Bonso A, Piccolo E (1990) Usefulness of head-up tilt test in evaluating patients with syncope of unknown origin and negative electrophysiologic study. Am J Cardiol 65: 1322–1327PubMedCrossRefGoogle Scholar
  53. 56.
    Perna GP, Ficola U, Salvatori MP, Stanislao M, Vigna C, Vil-lella A, Russo A, Fernelli R Vittori PGP, Loperfido F (1990) Increase of plasma beta endorphins in vasodepressor syncope. Am J Cardiol 65: 929–930PubMedCrossRefGoogle Scholar
  54. 57.
    Rutter PC, Potocnik SJ, Ludbrook J (1987) Sympathoadrenal mechanisms in cardiovascular responses to naloxone after hemorrhage. Am J Physiol 252: H40 - H46PubMedGoogle Scholar
  55. 58.
    Morita H, Nishida Y, Motochigawa H, Uemura H, Hosomi, H, Vatner SF (1988) Opiate receptor mediated decrease in renal nerve activity during hypotensive hemorrhage in conscious rabbits. Circ Res 63: 165–172PubMedGoogle Scholar
  56. 59.
    Evans RG, Ludbrook J, Potocnik SJ (1989) Intracisternal naloxone and cardiac nerve blockade prevent vasodilatation during simulated hemorrhage in awake rabbits. J Physiol (Lond) 409: 1–14Google Scholar
  57. 60.
    Smith ML, Carlson MD, Thames MC (1993) Naloxone does not prevent vasovagal syncope during simulated orthostasis in humans. J Auton Nerv Syst 45: 1–9PubMedCrossRefGoogle Scholar
  58. 61.
    Kosinski D, Grubb BP, Temesy-Armos P (1994) The use of serotonin reuptake inhibitors in the treatment of neurally mediated cardiovascular disorders. J Serotonin Res 1: 85–90Google Scholar
  59. 62.
    Morgan DA, Thoren P, Wilczynski EA, Victor RG, Mark AL (1988) Serotonergic mechanisms mediate renal sympathoinhi-bition during severe hemorrhage in rats. Am J Physiol 255: H496 - H502PubMedGoogle Scholar
  60. 63.
    Brody MJ (1978) Histaminergic and cholinergic vasodilator systems. In: Vanhoutte PM, Leusen I (eds) Mechanisms of vasodilatation. Karger, Basel, pp 266–277Google Scholar
  61. 64.
    Kellogg DL, Johnson JM, Kosiba WA (1990) Baroreflex control of the cutaneous active vasodilator system in humans. Circ Res 66: 1420–1426PubMedGoogle Scholar
  62. 65.
    Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24: 509–581PubMedGoogle Scholar
  63. 66.
    Bevan JA, Brayden JE (1987) Nonadrenergic neural vasodilator mechanisms. Circ Res 60: 309–326PubMedGoogle Scholar
  64. 67.
    Warner MR, Levy MN (1989) Inhibition of cardiac vagal effects by neurally released and exogenous neuropeptide Y. Circ Res 65: 1536–1546PubMedGoogle Scholar
  65. 68.
    Lippman L, Stein KM, Lerman BB (1995) Failure to decrease parasympathetic tone during upright tilt predicts a positive tilt table test. Am J Cardiol 75: 591–595PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1996

Authors and Affiliations

  • D. G. Benditt
    • 1
  • K. G. Lurie
    • 1
  • S. W. Adler
    • 1
  1. 1.Cardiac Arrhythmia and Syncope Centers, Department of Medicine (Cardiovascular Division)University of Minnesota Medical SchoolMinneapolisUSA

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