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CLINICAL RESEARCH

Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response

Janneke Gisolf, MSc^*,*, Berend E. Westerhof, MSc, Nynke van Dijk, MD, Karel H. Wesseling, MSc, Wouter Wieling, MD, PhD and John M. Karemaker, PhD^*

^* Department of Physiology, Academic Medical Center, Cardiovascular Research Institute, AmsterdamNetherlands
TNO-TPD-BMI, Academic Medical Center, Cardiovascular Research Institute, AmsterdamNetherlands
Department of Internal Medicine, Academic Medical Center, Cardiovascular Research Institute, Amsterdam, Netherlands
Finapres Medical Systems, Amsterdam, the Netherlands

Manuscript received March 15, 2004; revised manuscript received March 26, 2004, accepted April 6, 2004.

^* Reprint requests and correspondence: Ms. Janneke Gisolf, Department of Physiology, Room M01-07, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, the Netherlands.
j.gisolf{at}amc.uva.nl

OBJECTIVES: 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.

Abbreviations and Acronyms   BRS = baroreflex sensitivity   CO = cardiac output   DAP = diastolic arterial pressure   HR = heart rate   IBI = interbeat interval   MAP = mean arterial pressure   NO = nitric oxide   NTG = nitroglycerin   SAP = systolic arterial pressure   SNP = sodium nitroprusside   SV = stroke volume   SVR = systemic vascular resistance   VVS = vasovagal syncope

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