This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Theodorakis, G. N. Articles by Kremastinos, D. T. Search for Related Content PubMed PubMed Citation Articles by Theodorakis, G. N. Articles by Kremastinos, D. T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Fainting Hazardous Substances DB HYDROCORTISONE

(Circulation. 1998;98:2724-2730.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Central Serotonergic Responsiveness in Neurocardiogenic Syncope

A Clomipramine Test Challenge

George N. Theodorakis, MD; Manolis Markianos, PhD; Efthimios G. Livanis, MD; Elias Zarvalis, MD; Panagiota Flevari, MD; Dimitrios T. Kremastinos, MD

From the 2nd Department of Cardiology, Onassis Cardiac Surgery Center (G.N.T., E.G.L., E.Z., P.F., D.T.K.) and Laboratory of Clinical Neurochemistry (M.M.), Eginition Hospital, Athens University Medical School, Athens, Greece.

Correspondence to George N. Theodorakis, MD, Onassis Cardiac Surgery Center, 2nd Department of Cardiology, 356 Sygrou Ave, 176 74 Athens, Greece. E-mail elbee{at}ath.forthnet.gr

Background—Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine.

Methods and Results—Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47±18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49±10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3±7.2 vs 9.3±7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172±15 vs 118±21 ng/mL P=0.04) and at 45 minutes (189±20 vs 116±23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results.

Conclusions—Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.

Key Words: syncope • brain • transplantation • nervous system

This article has been cited by other articles:

				J. C. Guzman, R. G. Garcia, R. Dillenburg, F. S. Sieger, P. Lopez-Jaramillo, and C. A. Morillo Central serotoninergic response to orthostatic challenge in patients with neurocardiogenic syncope. Europace, April 1, 2006; 8(4): 306 - 311. [Abstract] [Full Text] [PDF]

				G. N. Theodorakis, D. Leftheriotis, E. G. Livanis, P. Flevari, G. Karabela, N. Aggelopoulou, and D. Th. Kremastinos Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Europace, March 1, 2006; 8(3): 193 - 198. [Abstract] [Full Text] [PDF]

				G.N. Theodorakis, E.G. Livanis, D. Leftheriotis, P. Flevari, M. Markianos, and D.Th. Kremastinos Head-up tilt test with clomipramine challenge in vasovagal syndrome--a new tilt testing protocol Eur. Heart J., April 1, 2003; 24(7): 658 - 663. [Abstract] [Full Text] [PDF]

				D. I. Leftheriotis, G. N. Theodorakis, and D. Th. Kremastinos Prolonged asystole during head-up tilt testing with clomipramine infusion Europace, January 1, 2003; 5(3): 313 - 315. [Abstract] [Full Text] [PDF]

				P. Flevari, E. G. Livanis, G. N. Theodorakis, E. Zarvalis, T. Mesiskli, and D. T. h Kremastinos Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well-being J. Am. Coll. Cardiol., August 7, 2002; 40(3): 499 - 504. [Abstract] [Full Text] [PDF]

				G. N. Theodorakis, M. Markianos, E. Zarvalis, E. G. Livanis, P. Flevari, and D. T. Kremastinos Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome J. Am. Coll. Cardiol., July 1, 2000; 36(1): 174 - 178. [Abstract] [Full Text] [PDF]

				A. P. Fitzpatrick and A. Zaidi Tilt methodology in reflex syncope: emerging evidence J. Am. Coll. Cardiol., July 1, 2000; 36(1): 179 - 180. [Full Text] [PDF]

				P. Alboni, M. Bondanelli, M. Dinelli, P. Gruppillo, P. Franceschetti, P. Marchi, and E.C. degli Uberti Role of the serotonergic system in the genesis of vasovagal syncope Europace, January 1, 2000; 2(2): 172 - 180. [Abstract] [PDF]

				S.W. Parry and R.A. Kenny The management of vasovagal syncope QJM, December 1, 1999; 92(12): 697 - 705. [Full Text] [PDF]