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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Nov 15;102(10):1824–1830. doi: 10.1172/JCI3050

Yohimbine in neurally mediated syncope. Pathophysiological implications.

R Mosqueda-Garcia 1, R Fernandez-Violante 1, J Tank 1, M Snell 1, G Cunningham 1, R Furlan 1
PMCID: PMC509132  PMID: 9819368

Abstract

In this study, we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncope (NMS) by manipulating overall sympathetic outflow in subjects susceptible to tilt-induced syncope. Eight previously characterized patients with recurrent NMS (five females and three males; 34+/-2 yr) were recruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent initial administration of clonidine (CLO) or yohimbine (YHO). This was done, prospectively, to determine doses of these agents that would increase or decrease plasma norepinephrine levels by >/= 30%. On a different day, in all subjects we determined intraarterial blood pressure, EKG and muscle sympathetic nerve activity (MSNA) both supine and during upright tilt. After this, subjects randomly received either CLO or YHO, and 3 h later another tilt was performed. After 1 wk, a similar procedure with the other drug was performed. During the two basal tilts, all the control subjects completed the study, whereas all the NMS patients developed syncope. Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in three out of eight controls and in all the NMS patients. In contrast, YHO not only increased basal plasma NorEpi levels and MSNA, but also prevented syncope in seven out of eight patients. In a selected population of patients, increased sympathetic activity is not a prerequisite for the development of syncope. Yohimbine-induced enhancement of sympathetic tone in patients with NMS improves orthostatic tolerance and raises the possibility that this drug may be a useful agent in the treatment of NMS.

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Selected References

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  1. Abboud F. M. Neurocardiogenic syncope. N Engl J Med. 1993 Apr 15;328(15):1117–1120. doi: 10.1056/NEJM199304153281510. [DOI] [PubMed] [Google Scholar]
  2. Abi-Samra F., Maloney J. D., Fouad-Tarazi F. M., Castle L. W. The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin. Pacing Clin Electrophysiol. 1988 Aug;11(8):1202–1214. doi: 10.1111/j.1540-8159.1988.tb03973.x. [DOI] [PubMed] [Google Scholar]
  3. Almquist A., Goldenberg I. F., Milstein S., Chen M. Y., Chen X. C., Hansen R., Gornick C. C., Benditt D. G. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med. 1989 Feb 9;320(6):346–351. doi: 10.1056/NEJM198902093200603. [DOI] [PubMed] [Google Scholar]
  4. Almquist A., Goldenberg I. F., Milstein S., Chen M. Y., Chen X. C., Hansen R., Gornick C. C., Benditt D. G. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med. 1989 Feb 9;320(6):346–351. doi: 10.1056/NEJM198902093200603. [DOI] [PubMed] [Google Scholar]
  5. Bernardi L., Salvucci F., Leuzzi S., Radaelli A., Calciati A., Valle F., Savasta S., Scaramuzza A., Lorini R. Cardiovascular reflex changes preceding episodes of vasovagal syncope in paediatric subjects. Clin Sci (Lond) 1996;91 (Suppl):25–27. doi: 10.1042/cs0910025supp. [DOI] [PubMed] [Google Scholar]
  6. Chen M. Y., Goldenberg I. F., Milstein S., Buetikofer J., Almquist A., Lesser J., Benditt D. G. Cardiac electrophysiologic and hemodynamic correlates of neurally mediated syncope. Am J Cardiol. 1989 Jan 1;63(1):66–72. doi: 10.1016/0002-9149(89)91077-1. [DOI] [PubMed] [Google Scholar]
  7. Davis S. N., Shavers C., Costa F., Mosqueda-Garcia R. Role of cortisol in the pathogenesis of deficient counterregulation after antecedent hypoglycemia in normal humans. J Clin Invest. 1996 Aug 1;98(3):680–691. doi: 10.1172/JCI118839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fitzpatrick A. P., Banner N., Cheng A., Yacoub M., Sutton R. Vasovagal reactions may occur after orthotopic heart transplantation. J Am Coll Cardiol. 1993 Apr;21(5):1132–1137. doi: 10.1016/0735-1097(93)90235-s. [DOI] [PubMed] [Google Scholar]
  9. Fitzpatrick A., Theodorakis G., Vardas P., Kenny R. A., Travill C. M., Ingram A., Sutton R. The incidence of malignant vasovagal syndrome in patients with recurrent syncope. Eur Heart J. 1991 Mar;12(3):389–394. doi: 10.1093/oxfordjournals.eurheartj.a059906. [DOI] [PubMed] [Google Scholar]
  10. Goldberg M. R., Robertson D. Yohimbine: a pharmacological probe for study of the alpha 2-adrenoreceptor. Pharmacol Rev. 1983 Sep;35(3):143–180. [PubMed] [Google Scholar]
  11. Hackel A., Linzer M., Anderson N., Williams R. Cardiovascular and catecholamine responses to head-up tilt in the diagnosis of recurrent unexplained syncope in elderly patients. J Am Geriatr Soc. 1991 Jul;39(7):663–669. doi: 10.1111/j.1532-5415.1991.tb03619.x. [DOI] [PubMed] [Google Scholar]
  12. Hayoz D., Noll G., Passino C., Weber R., Wenzel R., Bernardi L. Progressive withdrawal of muscle nerve sympathetic activity preceding vaso-vagal syncope during lower-body negative pressure. Clin Sci (Lond) 1996;91 (Suppl):50–51. doi: 10.1042/cs0910050supp. [DOI] [PubMed] [Google Scholar]
  13. Jellema W. T., Imholz B. P., van Goudoever J., Wesseling K. H., van Lieshout J. J. Finger arterial versus intrabrachial pressure and continuous cardiac output during head-up tilt testing in healthy subjects. Clin Sci (Lond) 1996 Aug;91(2):193–200. doi: 10.1042/cs0910193. [DOI] [PubMed] [Google Scholar]
  14. Mark A. L. The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. J Am Coll Cardiol. 1983 Jan;1(1):90–102. doi: 10.1016/s0735-1097(83)80014-x. [DOI] [PubMed] [Google Scholar]
  15. McAuley D., Silke B., Farrell S. Reliability of blood pressure determination with the Finapres with altered physiological states or pharmacodynamic conditions. Clin Auton Res. 1997 Aug;7(4):179–184. doi: 10.1007/BF02267979. [DOI] [PubMed] [Google Scholar]
  16. Morillo C. A., Eckberg D. L., Ellenbogen K. A., Beightol L. A., Hoag J. B., Tahvanainen K. U., Kuusela T. A., Diedrich A. M. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation. 1997 Oct 21;96(8):2509–2513. doi: 10.1161/01.cir.96.8.2509. [DOI] [PubMed] [Google Scholar]
  17. Morita H., Vatner S. F. Effects of hemorrhage on renal nerve activity in conscious dogs. Circ Res. 1985 Nov;57(5):788–793. doi: 10.1161/01.res.57.5.788. [DOI] [PubMed] [Google Scholar]
  18. Mosqueda-Garcia R., Furlan R., Fernandez-Violante R., Desai T., Snell M., Jarai Z., Ananthram V., Robertson R. M., Robertson D. Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. J Clin Invest. 1997 Jun 1;99(11):2736–2744. doi: 10.1172/JCI119463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Novak V., Honos G., Schondorf R. Is the heart "empty' at syncope? J Auton Nerv Syst. 1996 Aug 27;60(1-2):83–92. doi: 10.1016/0165-1838(96)00040-9. [DOI] [PubMed] [Google Scholar]
  20. Rea R. F., Biaggioni I., Robertson R. M., Haile V., Robertson D. Reflex control of sympathetic nerve activity in dopamine beta-hydroxylase deficiency. Hypertension. 1990 Jan;15(1):107–112. doi: 10.1161/01.hyp.15.1.107. [DOI] [PubMed] [Google Scholar]
  21. Robertson D., Johnson G. A., Robertson R. M., Nies A. S., Shand D. G., Oates J. A. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation. 1979 Apr;59(4):637–643. doi: 10.1161/01.cir.59.4.637. [DOI] [PubMed] [Google Scholar]
  22. Scherrer U., Vissing S., Morgan B. J., Hanson P., Victor R. G. Vasovagal syncope after infusion of a vasodilator in a heart-transplant recipient. N Engl J Med. 1990 Mar 1;322(9):602–604. doi: 10.1056/NEJM199003013220906. [DOI] [PubMed] [Google Scholar]
  23. Sidery M. B., Macdonald I. A. Blood pressure changes associated with tilting in normotensive subjects: differences in response pattern as measured by oscillometry and auscultation. Clin Auton Res. 1991 Jun;1(2):161–166. doi: 10.1007/BF01826214. [DOI] [PubMed] [Google Scholar]
  24. Sra J. S., Murthy V., Natale A., Jazayeri M. R., Dhala A., Deshpande S., Sheth M., Akhtar M. Circulatory and catecholamine changes during head-up tilt testing in neurocardiogenic (vasovagal) syncope. Am J Cardiol. 1994 Jan 1;73(1):33–37. doi: 10.1016/0002-9149(94)90723-4. [DOI] [PubMed] [Google Scholar]
  25. Stokes D. N., Clutton-Brock T., Patil C., Thompson J. M., Hutton P. Comparison of invasive and non-invasive measurements of continuous arterial pressure using the Finapres. Br J Anaesth. 1991 Jul;67(1):26–35. doi: 10.1093/bja/67.1.26. [DOI] [PubMed] [Google Scholar]
  26. WAYNE H. H. Syncope. Physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med. 1961 Mar;30:418–438. doi: 10.1016/0002-9343(61)90051-1. [DOI] [PubMed] [Google Scholar]
  27. Wallin B. G., Sundlöf G. Sympathetic outflow to muscles during vasovagal syncope. J Auton Nerv Syst. 1982 Nov;6(3):287–291. doi: 10.1016/0165-1838(82)90001-7. [DOI] [PubMed] [Google Scholar]
  28. Waxman M. B., Yao L., Cameron D. A., Wald R. W., Roseman J. Isoproterenol induction of vasodepressor-type reaction in vasodepressor-prone persons. Am J Cardiol. 1989 Jan 1;63(1):58–65. doi: 10.1016/0002-9149(89)91076-x. [DOI] [PubMed] [Google Scholar]
  29. van Lieshout J. J., Wieling W., Karemaker J. M., Eckberg D. L. The vasovagal response. Clin Sci (Lond) 1991 Nov;81(5):575–586. doi: 10.1042/cs0810575. [DOI] [PubMed] [Google Scholar]

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