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. 1997 Jun 1;99(11):2736–2744. doi: 10.1172/JCI119463

Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt.

R Mosqueda-Garcia 1, R Furlan 1, R Fernandez-Violante 1, T Desai 1, M Snell 1, Z Jarai 1, V Ananthram 1, R M Robertson 1, D Robertson 1
PMCID: PMC508120  PMID: 9169504

Abstract

The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1 episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy subjects who consistently experienced syncope during tilt (FS+, n = 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS+ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope.

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Selected References

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  1. 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]
  2. Baharav A., Mimouni M., Lehrman-Sagie T., Izraeli S., Akselrod S. Spectral analysis of heart rate in vasovagal syncope: the autonomic nervous system in vasovagal syncope. Clin Auton Res. 1993 Aug;3(4):261–269. doi: 10.1007/BF01829016. [DOI] [PubMed] [Google Scholar]
  3. Chosy J. J., Graham D. T. Catecholamines in vasovagal fainting. J Psychosom Res. 1965 Oct;9(2):189–194. doi: 10.1016/0022-3999(65)90032-2. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Eckberg D. L., Harkins S. W., Fritsch J. M., Musgrave G. E., Gardner D. F. Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients. J Clin Invest. 1986 Aug;78(2):366–374. doi: 10.1172/JCI112586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Esler M., Jennings G., Lambert G., Meredith I., Horne M., Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev. 1990 Oct;70(4):963–985. doi: 10.1152/physrev.1990.70.4.963. [DOI] [PubMed] [Google Scholar]
  7. Ferguson J. J. American College of Cardiology 45th Annual Scientific Session, Orlando, Florida, March 24 to 27, 1996. Circulation. 1996 Jul 1;94(1):1–5. doi: 10.1161/01.cir.94.1.1. [DOI] [PubMed] [Google Scholar]
  8. Ferguson J. J. American College of Cardiology 45th Annual Scientific Session, Orlando, Florida, March 24 to 27, 1996. Circulation. 1996 Jul 1;94(1):1–5. doi: 10.1161/01.cir.94.1.1. [DOI] [PubMed] [Google Scholar]
  9. Ferguson J. J. American College of Cardiology 45th Annual Scientific Session, Orlando, Florida, March 24 to 27, 1996. Circulation. 1996 Jul 1;94(1):1–5. doi: 10.1161/01.cir.94.1.1. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. GLICK G., YU P. N. Hemodynamic changes during spontaneous vasovagal reactions. Am J Med. 1963 Jan;34:42–51. doi: 10.1016/0002-9343(63)90037-8. [DOI] [PubMed] [Google Scholar]
  12. Goldstein D. S., Spanarkel M., Pitterman A., Toltzis R., Gratz E., Epstein S., Keiser H. R. Circulatory control mechanisms in vasodepressor syncope. Am Heart J. 1982 Nov;104(5 Pt 1):1071–1075. doi: 10.1016/0002-8703(82)90442-2. [DOI] [PubMed] [Google Scholar]
  13. Greenfield A. D. Survey of the evidence for active neurogenic vasodilatation in man. Fed Proc. 1966 Nov-Dec;25(6):1607–1610. [PubMed] [Google Scholar]
  14. Jacobs M. C., Goldstein D. S., Willemsen J. J., Smits P., Thien T., Dionne R. A., Lenders J. W. Neurohumoral antecedents of vasodepressor reactions. Eur J Clin Invest. 1995 Oct;25(10):754–761. doi: 10.1111/j.1365-2362.1995.tb01954.x. [DOI] [PubMed] [Google Scholar]
  15. Kapoor W. N., Smith M. A., Miller N. L. Upright tilt testing in evaluating syncope: a comprehensive literature review. Am J Med. 1994 Jul;97(1):78–88. doi: 10.1016/0002-9343(94)90051-5. [DOI] [PubMed] [Google Scholar]
  16. Kaufmann H. Neurally mediated syncope: pathogenesis, diagnosis, and treatment. Neurology. 1995 Apr;45(4 Suppl 5):S12–S18. [PubMed] [Google Scholar]
  17. Lepicovska V., Novak P., Nadeau R. Time-frequency dynamics in neurally mediated syncope. Clin Auton Res. 1992 Oct;2(5):317–326. doi: 10.1007/BF01824302. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Morillo C. A., Klein G. J., Jones D. L., Yee R. Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope. Am J Cardiol. 1994 Dec 15;74(12):1258–1262. doi: 10.1016/0002-9149(94)90559-2. [DOI] [PubMed] [Google Scholar]
  20. Mosqueda-Garcia R., Tseng C. J., Appalsamy M., Robertson D. Cardiovascular effects of microinjection of angiotensin II in the brainstem of renal hypertensive rats. J Pharmacol Exp Ther. 1990 Oct;255(1):374–381. [PubMed] [Google Scholar]
  21. Murray R. H., Thompson L. J., Bowers J. A., Albright C. D. Hemodynamic effects of graded hypovolemia and vasodepressor syncope induced by lower body negative pressure. Am Heart J. 1968 Dec;76(6):799–811. doi: 10.1016/0002-8703(68)90266-4. [DOI] [PubMed] [Google Scholar]
  22. Niijima A. The effect of 2-deoxy-D-glucose and D-glucose on the efferent discharge rate of sympathetic nerves. J Physiol. 1975 Sep;251(1):231–243. doi: 10.1113/jphysiol.1975.sp011089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Pruvot E., Vesin J. M., Schlaepfer J., Fromer M., Kappenberger L. Autonomic imbalance assessed by heart rate variability analysis in vasovagal syncope. Pacing Clin Electrophysiol. 1994 Nov;17(11 Pt 2):2201–2206. doi: 10.1111/j.1540-8159.1994.tb03826.x. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Sander-Jensen K., Secher N. H., Astrup A., Christensen N. J., Giese J., Schwartz T. W., Warberg J., Bie P. Hypotension induced by passive head-up tilt: endocrine and circulatory mechanisms. Am J Physiol. 1986 Oct;251(4 Pt 2):R742–R748. doi: 10.1152/ajpregu.1986.251.4.R742. [DOI] [PubMed] [Google Scholar]
  28. Sanders J. S., Ferguson D. W. Profound sympathoinhibition complicating hypovolemia in humans. Ann Intern Med. 1989 Sep 1;111(5):439–441. doi: 10.7326/0003-4819-111-5-439. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Sra J. S., Jazayeri M. R., Avitall B., Dhala A., Deshpande S., Blanck Z., Akhtar M. Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. N Engl J Med. 1993 Apr 15;328(15):1085–1090. doi: 10.1056/NEJM199304153281504. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Sundlöf G., Wallin B. G. Human muscle nerve sympathetic activity at rest. Relationship to blood pressure and age. J Physiol. 1978 Jan;274:621–637. doi: 10.1113/jphysiol.1978.sp012170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vallbo A. B., Hagbarth K. E., Torebjörk H. E., Wallin B. G. Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. Physiol Rev. 1979 Oct;59(4):919–957. doi: 10.1152/physrev.1979.59.4.919. [DOI] [PubMed] [Google Scholar]
  34. Victor R. G., Thorén P., Morgan D. A., Mark A. L. Differential control of adrenal and renal sympathetic nerve activity during hemorrhagic hypotension in rats. Circ Res. 1989 Apr;64(4):686–694. doi: 10.1161/01.res.64.4.686. [DOI] [PubMed] [Google Scholar]
  35. Wallin B. G., Sundlöf G., Delius W. The effect of carotid sinus nerve stimulation on muscle and skin nerve sympathetic activity in man. Pflugers Arch. 1975 Jul 21;358(2):101–110. doi: 10.1007/BF00583921. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Waxman M. B., Cameron D. A., Wald R. W. Role of ventricular vagal afferents in the vasovagal reaction. J Am Coll Cardiol. 1993 Apr;21(5):1138–1141. doi: 10.1016/0735-1097(93)90236-t. [DOI] [PubMed] [Google Scholar]
  38. Weiss S., Wilkins R. W., Haynes F. W. THE NATURE OF CIRCULATORY COLLAPSE INDUCED BY SODIUM NITRITE. J Clin Invest. 1937 Jan;16(1):73–84. doi: 10.1172/JCI100840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yatomi A., Iguchi A., Uemura K., Sakamoto N., Iwase S., Mano T. A rare case of recurrent vasodepressive attacks of 2-hours duration: analysis of the mechanism by muscle sympathetic nerve activity recording. Clin Cardiol. 1989 Mar;12(3):164–168. doi: 10.1002/clc.4960120311. [DOI] [PubMed] [Google Scholar]
  40. Ziegler M. G., Echon C., Wilner K. D., Specho P., Lake C. R., McCutchen J. A. Sympathetic nervous withdrawal in the vasodepressor (vasovagal) reaction. J Auton Nerv Syst. 1986 Dec;17(4):273–278. doi: 10.1016/0165-1838(86)90093-7. [DOI] [PubMed] [Google Scholar]
  41. 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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