Skip to main content
Log in

The Potential Role of Serotonin in the Pathogenesis of Neurocardiogenic Syncope and Related Autonomic Disturbances

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Grubb BP. Neurocardiogenic syncope. In: Grubb BP, Olshansky B, eds. Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing, 1998;73-106.

    Google Scholar 

  2. Lewis T. Vasovagal syncope and the carotid sinus mechanism with comments on Gower's and Nothnagel's syndrome. Br Med J 1932;1:873-876.

    Google Scholar 

  3. Kenny RA, Ingram A, Bayliss J, Sutton R. Head up tilt: A useful test for investigating unexplained syncope. Lancet 1986;2:1352-1354.

    Google Scholar 

  4. Fitzpatrick A, Sutton R. Tilting toward a diagnosis in unexplained recurrent syncope. Lancet 1989;1:658-660.

    Google Scholar 

  5. Fitzpatrick A, Williams T, Ahmed R, et al. Echocardiographic and endocrine changes during vasovagal syncope induced by prolonged head up tilt. Eur J Cardiac Pacing Electrophysiol 1992;2:121-128.

    Google Scholar 

  6. Grubb BP, Gerard G, Roush K, et al. Cerebral vasoconstriction during head upright tilt-induced vasovagal syncope. Circulation 1991;84:1157-1164.

    Google Scholar 

  7. Rea R, Thames M. Neural control mechanisms and vasovagal syncope. J Cardiovasc Electrophysiol 1993;4:587-595.

    Google Scholar 

  8. Saxena PR. Historical aspects of 5-hydroxytryptamine, discovery and receptor classification. In: Olesen J, Saxena PR, eds. 5-hydroxytryptamine Mechanisms in Primary Headaches. New York: Raven Press, 1992;3-18.

    Google Scholar 

  9. Erspamer V. Pharmacology of indolealkylamines. Pharmacol Rev 1954;6:425-487.

    Google Scholar 

  10. Rapport MM, Green AA, Page IH. Serum vasoconstrictor (serotonin): Isolation and characterization. J Biol Chem 1948;176:1243-1251.

    Google Scholar 

  11. Bard P. Anatomical organization of the central nervous system in relation to control of the heart and blood vessels. Physiol Rev 1960;4:3-53.

    Google Scholar 

  12. Dahlström A, Fuxe K. Evidence for the existence of monomine neurons in the central nervous system. Acta Physiol Scand 1965;64:1-7.

    Google Scholar 

  13. Jacobs B, Azmitia E. Structure and function of the brain serotonin system. Physiol Rev 1992;72:165-229.

    Google Scholar 

  14. Benarroch E. The central autonomic network: Functional organization, dysfunction, and perspective. Mayo Clin Proc 1993;68:988-1001.

    Google Scholar 

  15. Fuller RW. Neural functions of serotonin. Scientific American Sci Med 1995;4:48-57.

    Google Scholar 

  16. Fuller RW. New developments in serotonin pharmacology. In: Ruffo R, Hollinger M, eds. G Protein Coupled Trans-Membrane Signaling Mechanisms. Boca Raton, Florida: CRC Press, 1995.

    Google Scholar 

  17. Boadle-Biber MC. Regulation of serotonin synthesis. Prog Biophys Molec Biol 1993;60:1-15.

    Google Scholar 

  18. Silberstein SD. Serotonin (5-HT) and migraine headache. Headache 1994;34:408-417.

    Google Scholar 

  19. Gonzales-Heydrich J, Peroutka S. Serotonin receptor and reuptake sites: Pharmacologic significance. J Clin Psychiatry 1990;51:5-12.

    Google Scholar 

  20. Hoyer D. International union of pharmacology classifications of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994;46:157-203.

    Google Scholar 

  21. Kuhn D, Wolfe W, Loyenburg W. Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 1980;2:243-255.

    Google Scholar 

  22. Baum T, Shropshire AT. Inhibition of efferent sympathetic nerve activity by 5-hydroxytryptophan in centrally administered 5-hydroxytryptamine. Neuropharmacology 1975;14: 227-233.

    Google Scholar 

  23. Tadepelli A, Mills E, Schanberg S. Central depressor of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: Influence of the supra-molecular areas of the brain. J Pharmacol Exper Therap 1977;202:310-319.

    Google Scholar 

  24. Strasberg B, Jagie A, Erdmann S et al. Carotid sinus hypersensitivity and the carotid sinus syndrome. Prog Cardiovasc Dis 1989;5:379-385.

    Google Scholar 

  25. Antonaccio MJ, Robson RD. Centrally-mediated cardiovascular effects of 5-hydroxytryptophan in MAO-inhibited dogs: Modification by autonomic antagonists. Arch Intern Pharmacodynamics 1975;213:200-210.

    Google Scholar 

  26. Chosy JJ, Graham DT. Catecholamines in vasovagal fainting. J Psychosomatic Res 1965;9:189-194.

    Google Scholar 

  27. Sra J. Jazayeri M. Murthy V et al. Sequential catecholamine changes during upright tilt: Possible hormonal mechanisms responsible for pathogenesis of neurocardiogenic syncope. J Am Coll Cardiol 1991;17:216A (Abstract).

    Google Scholar 

  28. Lewis W, Smith M, Carlson M. Peripheral sympathoinhibition precedes hypotension and bradycardia during neurally-mediated vasovagal syncope. PACE 1994;17:747. (Abstract).

    Google Scholar 

  29. Skoog P, Mansson J. Theen P. Changes in renal sympathetic outflow during hypotensive hemorrhage in rats. Acta Physiol Scand 1985;125:655-660.

    Google Scholar 

  30. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol (Heart Circ Physiol 29) 1991;260:H305-H308.

    Google Scholar 

  31. Morgan DA, Thoren P, Wilczynski E et al. Serotonergic mechanisms mediate renal sympatho-inhibition during severe hemorrhage in rats.AmJ Physiol 1988;255:H496–H502.

    Google Scholar 

  32. Elam RF, Bergman F, Feverstein G. The use of antiserotonergic agents for the treatment of acute hemorrhagic shock in cats. Eur J Pharmacol 1985;107:275-278.

    Google Scholar 

  33. Hasser E, Schadt J, Grove K. Serotonergic and apioid interactions during acute hemorrhagic hypotension in the conscious rabbit. FASEB J 1989;3:A1014. (Abstract).

    Google Scholar 

  34. Evans RG, Kapoor V, Ludbrook J. A CNS serotonergic mechanism in acute central hypovolemia in conscious rabbits? J Cardiovasc Pharmacol 1992;19(6):1009-1017.

    Google Scholar 

  35. Abboud FM. Neurocardiogenic syncope. N Engl J Med 1993;328:1117-1119.

    Google Scholar 

  36. Matzen S, Secher NH, Knigge U, et al. Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head up tilt in humans. Acta Physiol Scand 1993;149:163-176.

    Google Scholar 

  37. Theodorakis G, Markianos M, Sourlas N, et al. Central serotonergic and beta adrenergic activity in patients with vasovagal syncope. Circulation 1995;92:414.

    Google Scholar 

  38. Theodorakis G, Flevari P, Livanis E, et al. Clomipramine challenge during tilt test and central serotonergic activity. Circulation 1997;96:221.

    Google Scholar 

  39. Lehnert H, Lombardi F, Raeder E, et al. Increased release of brain serotonin reduces vulnerability of ventricular fibrillation in the cat. J Cardiovasc Pharmacol 1987;10:389-397.

    Google Scholar 

  40. Verrier R. Neurochemical approaches to the prevention of ventricular fibrillation. Federation Proc 1986;45:2191-2196.

    Google Scholar 

  41. Lown B, Verrier RL. Neural activity and ventricular fibrillation. N Engl J Med 1976;294:1165-1170.

    Google Scholar 

  42. Rabinowitz SH, Lown B. Central neurochemical factors related to serotonin metabolism and cardiac vulnerability for repetitive electrical activity. Am J Cardiol 1978;41:516-522.

    Google Scholar 

  43. Blatt CM, Rabinowitz SH, Lown B. Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium. Circ Res 1979;44:723-730.

    Google Scholar 

  44. Rickels K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry 1990;51:9-12.

    Google Scholar 

  45. Fuller RW, Wong DT. Serotonin reuptake blockers in vitro and in vivo. J Clin Psychopharmacol 1987;7:445-495.

    Google Scholar 

  46. Delgado P. Serotonin and the neurobiology of major depression. Psychopharmacol Bull 1991;27:321-330.

    Google Scholar 

  47. Preskorn SH. Pharmacokinetics of antidepressants. J Clin Psychiatry 1993;54:14-34.

    Google Scholar 

  48. Fontaine R, Ontiveros A, Elie R et al. A double blind trial of nefazodone, imipramine and placebo in major depression. J Clin Psychiatry 1994,55:234-241.

    Google Scholar 

  49. Hjorth S, Sharp T. In vivo microdialysis evidence for central serotonin 1A and 1B autoreceptor of the beta receptor antagonist penbutolol. J Pharmacol Exp Therap 1993:265:707-712.

    Google Scholar 

  50. Hjorth S. Penbutolol as a blocker of central 5-HY1A receptor mediated responses. Eur J Pharmacol 1992;222:121-127.

    Google Scholar 

  51. Meltzer HY, Maes M. Effect of pindolol on the L-5HTP-induced increase in plasma and cortisol concentrations in man. Psychopharmacology 1994;114:635-643.

    Google Scholar 

  52. Artigas F, Perez V, Alvarez E. Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitos. Arch Gen Psychiatry 1994;51:148-251.

    Google Scholar 

  53. Kosinski D, Grubb BP, Temesy-Armos P. Pathophysiological aspects of neurocardiogenic syncope. PACE 1995;18:716-724.

    Google Scholar 

  54. Sutton R, Petersen M. The clinical spectrum of neurocardiogenic syncope. J Cardiovasc Eletrophysiol 1995;6:569-576.

    Google Scholar 

  55. Grubb BP, Wolfe D, Samoil D, et al. Usefulness of fluoxetine hydrochloride for prevention of upright tilt-induced syncope. PACE 1992;15:742-748.

    Google Scholar 

  56. Grubb BP, Samoil D, Kosinski D, et al. Use of sertraline hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994;24:490-492.

    Google Scholar 

  57. Dan D, Grubb BP, Mouhaffel A, et al. Preliminary observations on the use of nefazodone, a new selective 5-HT2A receptor blocker in the treatment of neurally mediated syncope. Eur J Card Pace Electrophysiol 1996;6:89-94.

    Google Scholar 

  58. Williamson BD, Strickberger A, Ching Man K, et al. A randomized trial of sertraline versus atenolol and disopyramide in the treatment of neurocardiogenic syncope. PACE 1994; 17:747. (Abstract).

    Google Scholar 

  59. Constantin L, Martins JB, Fincham RW, et al. Bradycardia and syncope as manifestations of partial epilepsy. J Am Coll Cardiol 1990;15:900-905.

    Google Scholar 

  60. Löfring V. Cardiovascular adjustments induced from the rostral cingulate gyrus, with specific reference to sympathoinhibiting mechanisms. Acta Physiol Scand 1961;54(Suppl 184):55-82.

    Google Scholar 

  61. Crippen D. Stress, agitation and brain failure in critical care medicine. Crit Care Q 1992;15:52-74.

    Google Scholar 

  62. Crippen D. Understanding the neurohumoral causes of anxiety in the ICU. J Crit Illness 1995;10(8):550-560.

    Google Scholar 

  63. Kenny RA, Traynor G. Carotid sinus syndrome—clinical characteristics in elderly patients. Age and Aging 1991;20: 449-454.

    Google Scholar 

  64. Almquist A, Gormick C, Benson W, et al. Carotid sinus hypersensitivity: Evaluation of the vasodepressor component. Circulation 1985;71:5:927-936.

    Google Scholar 

  65. Zee-Cheng CS, Gibbs HR. Pure vasodepressor carotid sinus hypersensitivity.Am J Med 1986;1095-1097.

  66. Grubb BP, Samoil D, Kosinski D, et al. The use of serotonin reuptake inhibitors for the treatment of recurrent syncope due to carotid sinus hypersensitivity unresponsive to dual chamber cardiac pacing. PACE 1994;17:1434-1436.

    Google Scholar 

  67. Dan D, Grubb BP, Mouhaffel A, Kosinski D. Use of serotonin reuptake inhibitors as a primary therapy for carotid sinus hypersensitivity. PACE 1997;20:1633-1735.

    Google Scholar 

  68. Pilgrim J, Stansfeld S, Marmot M. Low pressure, low mood? Br Med J 1992;304:75-78.

    Google Scholar 

  69. Barrett-Conner E, Palinkas L. Low blood pressure and depression in older men: A population based study. Br Med J 1994;308:446-448.

    Google Scholar 

  70. Grubb BP. Dysautonomic syncope. In: Grubb BP, Olshansky B, eds. Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing, 1998;107-126.

    Google Scholar 

  71. Grubb BP, Samoil D, Kosinski D, Wolfe DA. Fluoxetine hydrochloride for the treatment of severe refractory orthostatic hypotension. Am J Med 1994;97:366-368.

    Google Scholar 

  72. Grubb BP, Kosinski D. Preliminary observations on the effects of venlafaxine hydrochloride in the treatment of severe refractory orthostatic hypotension. J Serotonin Res 1996;3: 85-89.

    Google Scholar 

  73. Dheenan S, Venkatesan J, Grubb BP, Henrich W. Effect of sertraline hydrochloride on dialysis hypotension. Am J Kidney Dis 1998;31:624-630.

    Google Scholar 

  74. Grubb BP, Kosinski D. Serotonin and syncope: An emerging connection? Eur J Cardiac Pacing Electrophysiol 1996;5: 306-314.

    Google Scholar 

  75. Azmitia EC, Whitaker-Azmitia PM. Awakening the sleeping giant: Anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry 1991;52:4-16.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grubb, B.P., Karas, B.J. The Potential Role of Serotonin in the Pathogenesis of Neurocardiogenic Syncope and Related Autonomic Disturbances. J Interv Card Electrophysiol 2, 325–332 (1998). https://doi.org/10.1023/A:1009792000490

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009792000490

Keywords

Navigation