title: Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response.
abstract: OBJECTIVE
  We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR).
  
  
  BACKGROUND
  Nitroglycerin is used in tilt testing to elicit a vasovagal response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control.
  
  
  METHODS
  Routine tilt testing was conducted in 39 patients with suspected vasovagal syncope (age 36 +/- 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains.
  
  
  RESULTS
  During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p < 0.001), whereas SVR and HR increased (p < 0.001) in all patients. Arterial pressure was initially maintained. Baroreflex sensitivity decreased after NTG. On Cox regression analysis, the occurrence of a vasovagal response was related to a drop in SV after NTG (hazard ratio 0.86, p = 0.005).
  
  
  CONCLUSIONS
  The cardiovascular response to NTG is similar in vasovagal and non-vasovagal patients, but more pronounced in those with tilt-positive results. The NTG-facilitated presyncope appears to be CO-mediated, and there is no evidence of NTG-induced sympathetic inhibition.
authors.affiliation: Department of Physiology, Academic Medical Center, Cardiovascular Research Institute, Amsterdam, The Netherlands. j.gisolf@amc.uva.nl
authors.forename: Janneke
authors.initials: J
authors.lastname: Gisolf
authors.forename: Berend E
authors.initials: BE
authors.lastname: Westerhof
authors.forename: Nynke
authors.initials: N
authors.lastname: van Dijk
authors.forename: Karel H
authors.initials: KH
authors.lastname: Wesseling
authors.forename: Wouter
authors.initials: W
authors.lastname: Wieling
authors.forename: John M
authors.initials: JM
authors.lastname: Karemaker
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D017704:Baroreflex; D002302:Cardiac Output; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000009:adverse effects*; D016016:Proportional Hazards Models; D012107:Research Design; D019462:Syncope, Vasovagal / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D018667:Tilt-Table Test / Q000379:methods; D014655:Vascular Resistance
chemical_list: D005996:Nitroglycerin