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Supine and upright haemodynamic effects of
sublingual nitroglycerin and inhaled salbutamol: a
double-blind, placebo-controlled, randomized study
Anna M. Tahvanainen
a
, Antti J. Tikkakoski
a
, Miia H. Leskinen
a
, Klaus Nordhausen
b
,
Mika Ka ¨ ho ¨ nen
a,c
, Tiit Ko ¨o ¨ bi
c
, Jukka T. Mustonen
a,d
, and Ilkka H. Po ¨ rsti
a,d
Objectives: Pulse wave analysis is widely applied to
measure the haemodynamic effects of nitroglycerin
and salbutamol as an endothelium-independent
and endothelium-dependent vasodilator, respectively.
The recordings are usually performed in supine
position from 10 to 20 successive heartbeats without
simultaneous measurement of vascular resistance
and cardiac function. Our objective was to examine
the effects of nitroglycerin and salbutamol on
central haemodynamics, arterial stiffness, cardiac
function, and vascular resistance in supine and upright
positions.
Methods: A placebo-controlled, randomized and double-
blinded passive head-up tilt protocol was performed after
sublingual nitroglycerin (0.25 mg) or inhaled salbutamol
(400 mg) in 35 healthy volunteers. Continuous tonometric
pulse wave analysis, whole-body impedance cardiography,
and plethysmographic finger blood pressure recordings
were applied.
Results: Nitroglycerin decreased aortic and finger
blood pressure, radial DBP, vascular resistance,
augmentation index and pulse wave velocity, and
increased heart rate, cardiac index, stroke index and
aortic reflection time (P < 0.030 for all). Salbutamol
moderately decreased radial and aortic blood pressure and
finger DBP, augmentation index and vascular resistance,
but increased heart rate and cardiac index (P < 0.030 for
all). Almost all of the strong haemodynamic effects of
nitroglycerin were emphasized during the head-up tilt,
whereas the effects of salbutamol on heart rate and
cardiac index were more pronounced in the supine
position.
Conclusion: The haemodynamic changes induced by
nitroglycerin and salbutamol were dependent on body
position: the effects of nitroglycerin were accentuated
during the head-up tilt, whereas those of salbutamol were
more evident in the supine position.
Keywords: endothelium, haemodynamics, impedance
cardiography, pulse wave analysis, tilt-table test
Abbreviations: AIx, augmentation index; BP, blood
pressure; PWA, pulse wave analysis; PWV, pulse wave
velocity; SVRI, systemic vascular resistance index
INTRODUCTION
P
ulse wave analysis (PWA) has been widely applied
for the assessment of haemodynamics and endo-
thelial function in vivo [1,2]. In particular, changes in
the PWA-derived measure of wave reflection and arterial
stiffness, the augmentation index (AIx), have been utilized
to record the haemodynamic alterations induced by sub-
lingual nitroglycerin and inhaled salbutamol. The former
has served as an endothelium-independent agent and the
latter as a largely endothelium-dependent vasodilator, and
the changes induced by these compounds in PWA record-
ings have shown good repeatability [1,3]. Being noninva-
sive, easily accessible and repeatable, PWA has technical
benefits when compared with, for example, flow-mediated
dilatation and laborious invasive venous occlusion plethys-
mography [4,5]. Normally, the PWA measurements are
performed with the participant resting in supine position.
Parallel recordings of vascular resistance, pulse wave
velocity (PWV) and cardiac function have only seldom
been performed [6,7], although this would be important
as both nitroglycerin and salbutamol can influence these
variables.
Limited information about haemodynamics is obtained if
the variables are only measured at rest, as humans spend a
large part of their time in the upright position. The change
in body posture from supine to upright induces significant
changes in blood distribution, arterial resistance and auto-
nomic nervous system, and orthostatic challenge can thus
be regarded as an exercise test addressing cardiovascular
reactivity, as discussed in a recent editorial by Avolio and
Parati [8]. Previous reports have shown that the changes in
haemodynamic variables in response to physical challenge
have prognostic value. Enhanced blood pressure (BP)
Journal of Hypertension 2012, 30:297–306
a
School of Medicine,
b
School of Health Sciences, University of Tampere,
c
Department
of Clinical Physiology and
d
Department of Internal Medicine, Tampere University
Hospital, Tampere, Finland
Correspondence to Anna M. Tahvanainen, MD, Department of Internal Medicine,
School of Medicine, University of Tampere, Tampere FIN-33014, Finland. Tel: +358 3
3551 8306; fax: +358 3 3551 6164; e-mail: anna.tahvanainen@uta.fi
Received 15 June 2011 Revised 10 August 2011 Accepted 18 October 2011
J Hypertens 30:297–306 ß 2012 Wolters Kluwer Health | Lippincott Williams &
Wilkins.
DOI:10.1097/HJH.0b013e32834e4b26
Journal of Hypertension www.jhypertension.com 297
Original Article