Hypertension. 1995;26:520-523
(Hypertension. 1995;26:520-523.)
© 1995 American Heart Association, Inc.
Underestimation of Vasodilator Effects of Nitroglycerin by Upper Limb Blood Pressure
Kenji Takazawa;
Nobuhiro Tanaka;
Kazuhiro Takeda;
Fujio Kurosu;
Chiharu Ibukiyama
From the Second Department of Internal Medicine, Tokyo Medical College.
Correspondence to Kenji Takazawa, MD, The Second Department of Internal Medicine, Tokyo Medical College Hospital, 6-7-1, Nishishinjuku, Shinjuku, Tokyo 160, Japan.
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Abstract
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Abstract To determine why upper limb blood pressure
measurement
underestimates the vasodilator effects of
nitroglycerin on lowering
ascending aortic systolic
pressure, we studied 24 patients (58±11
years, mean±SD). Ascending
aortic pressure and radial
artery pulse calibrated by cuff blood
pressure measurement at
the brachial artery were recorded
simultaneously before and
5 minutes after sublingual
administration of 0.3 mg nitroglycerin.
Waves were
analyzed by a signal processor, and the fourth derivative
wave
was used to find the early (S1) and late (S2) systolic
shoulders (S1
corresponds to the second zero crossing and S2
to the third zero
crossing). Before nitroglycerin administration,
maximal
systolic pressure in the ascending aorta (141±21
mm Hg) coincided
with the late systolic peak in all patients,
and in most patients (21
of 24) maximal systolic pressure in
the radial artery (140±19 mm Hg)
coincided with the early
systolic peak. Maximal systolic pressure
decreased more in the
ascending aorta than in the radial artery (22±13
and
11±11 mm Hg, respectively;
P<.001). However, the
reduction
in the shoulder of late systolic pressure in the radial
artery
(24±13 mm Hg) clearly indicated the reduction in maximal
systolic
pressure (late systolic peak) in the ascending aorta. The
augmentation
index of the ratio of the height of late systolic pressure
to
early systolic pressure fell proportionally (
r=.74,
P<.001)
in the radial artery (from 0.88±0.13 to
0.60±0.11)
and in the ascending aorta (from 1.57±0.25 to 1.26±0.24),
which
indicated the reduction in late systolic pressures. These data
suggest
that ordinary peripheral artery blood pressure
measurement underestimates
the vasodilation effects of
nitroglycerin on the ascending aorta
because without
arterial pulse measurement it cannot show changes
in late
systolic pressure.
Key Words: vasodilator agents aorta, ascending blood pressure nitroglycerin
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Introduction
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Arterial pulse examinations have been
used since ancient times
for the diagnosis of various diseases and
physiological conditions.
1
Discrepancies of ascending aortic and upper limb systolic pressures
after
vasodilator agents have been reported
2 3 with regard
to differences
in maximal systolic pressure. These discrepancies were
caused
by the use of maximal systolic pressure for the assessment of
differences
in the pressure wave. Data on pulse waves in the literature
show
a reduction in the late systolic shoulders of upper limb pressure
waves,
but no numerical data concerning the late systolic shoulders
have
yet been introduced. The most important point is that systolic
pressure
has two components. We usually refer to systolic pressure as
maximal
systolic pressure. However, the maximal systolic pressures in
the
ascending aorta and brachial artery are completely different
in
terms of systolic timing. The ascending aortic pressure wave
can be
divided into two components at an early systolic inflection
point that
coincides with the ascending aortic flow peak.
4 The early
systolic component is mainly caused by ejection from
the left ventricle
and the late systolic component by the reflection
wave from the
periphery. These two components are transmitted
to
peripheral arteries undergoing certain modifications
according
to location and show characteristic waveforms. Maximal
systolic
pressure in the ascending aorta usually corresponds to the
late
systolic peak in adults, but maximal systolic pressure in the
brachial
artery corresponds to the early systolic peak. This is the
main
reason for the discrepancy between ascending aortic and brachial
arterial
systolic pressures.
The purpose of this study was to compare the differences of the early
and late systolic pressures in the ascending aorta and radial artery
with a newly developed automatic detection system and explore the
reasons why peripheral blood pressure measurements
underestimate the vasodilator effects of nitroglycerin
on lowering ascending aortic systolic pressure.
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Methods
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Twenty-four patients (21 men, 3 women) with a mean age of 58±11
years
(±SD) who underwent diagnostic cardiac
catheterization
were studied: 12 with myocardial
infarction, 9 with angina pectoris,
and 3 with chest pain syndrome
without organic cardiac abnormalities.
Ascending aortic pressure was
measured by a microtip catheter
(SVPC 684D, Millar Instruments) and
radial arterial pulse by
multisensor tonometry
(JENTOW-7000, Nippon Colin Co); both were
recorded
simultaneously on an FM tape recorder (XR-30, TEAC
Co)
and a chart recorder (MICOR, Siemens). Recordings were made
before
and after sublingual administration of 0.3 mg
nitroglycerin.
Waves were analyzed by a signal
processor (San-ei 7T-18A, Nippon
Electric Co) with a digital derivative
method. Waveforms of
the ascending aorta and radial artery were
digitized at 0.005-second
intervals and plotted from the first to the
fourth derivatives
of pressure waves. For smoothing of the waves,
smoothing points
of five points and five times averaging was used. The
final
frequency response of the derivative method was 8.16 Hz. The
algorithm
first found the peak and nadir of the pressure wave and then
determined
maximal systolic and diastolic pressures. If the
slope of the
fourth derivative wave corresponding to maximal systolic
pressure
is positive, this point is assigned as the time of the late
systolic
peak on the raw wave, and the second zero crossing from above
to
below is then used to determine the time of the early systolic
shoulder
on the raw wave. If the slope of the fourth derivative wave
corresponding
to maximal systolic pressure is negative, this point is
assigned
as the time of the early systolic peak on the raw wave, and
the
third zero crossing from below to above is then used to determine
the
time of the late systolic shoulder on the raw wave. The
augmentation
index was defined as the ratio of the height of the late
systolic
shoulder/peak to that of the early systolic shoulder/peak in
the
pulse. All procedures were approved by the ethics committee
of
Tokyo Medical College Hospital. Informed consent was obtained
from all
patients.
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Results
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Results of pressures and times before and after
nitroglycerin
are shown in the Table
,
with descriptive statistics and the
results of paired
t
tests. Maximal systolic pressure in the
radial artery coincided with
the early systolic peak in 21 patients
before
nitroglycerin and all 24 patients after
nitroglycerin.
Maximal systolic pressure decreased from
141±21 to 118±16
mm Hg in the ascending aorta and from 140±19 to
128±17
mm Hg in the radial artery. The reduction in maximal systolic
pressure
was greater in the ascending aorta (22±13 mm Hg) than
the
radial artery (11±11 mm Hg). The reduction in the
radial
arterial late systolic shoulder/peak was 24±13
mm Hg, and
there was no statistical difference compared with
the reduction in
maximal systolic pressure in the ascending
aorta. Fig 1
shows a sample tracing that reveals a marked reduction
in maximal
systolic pressure or late systolic peak in the ascending
aorta, but
maximal systolic pressure or early systolic peak
in the radial artery
did not change, with a marked reduction
in the late systolic
shoulder. Fig 2
shows how to identify the
shoulder/peak.
Fig 3
shows the relationship between the ascending
aortic
augmentation index (AoP-AI) and radial arterial
augmentation
index (RaP-AI). AoP-AI increased with increasing RaP-AI
(
r=.74,
P<.001).

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Figure 1. Tracings show results before and after
nitroglycerin (NTG) in a 58-year-old male subject.
After nitroglycerin the reduction in the late systolic
peak (dotted arrow) in the ascending aorta was equal to the reduction
in maximal systolic pressure. However, in the radial artery the late
systolic peak (dotted arrow) decreased with a minimal increase in the
early systolic peak (arrow), leading to no reduction in maximal
systolic pressure. The augmentation index in the radial artery (RaP-AI)
fell from 0.73 to 0.54 (from -27% to -46% of the original
augmentation index that Murgo et al5 first reported: the
ratio of [(Peak Late Systolic Pressure-Peak Early Systolic
Pressure)/Pulse Pressure (%)] is described in Fig 1 for comparison
with the present method). The ascending aortic augmentation index
(AoP-AI) decreased from 1.55 to 1.07 (from 36% to 7%). PTG indicates
plethysmogram at the finger tip; RaP, radial artery pressure in the
right arm; L.RaP, radial arterial pulse in the left arm
(not calibrated); AoP, ascending aortic pressure; and L.BraP, brachial
arterial pulse in the left arm (not calibrated).
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Figure 2. Tracings show identification of the first and
second systolic shoulders/peaks. Automatic detection of the
shoulders/peaks was developed for objective identification of the
points (see "Methods"). ECG indicates
electrocardiogram; AoP (top), ascending aortic
pressure; RaP (bottom), radial artery pressure; and NTG,
nitroglycerin. The first perpendicular line corresponds
to diastolic pressure, the second line to the early
systolic shoulder/peak, the third line to the late systolic
shoulder/peak, and the fourth line to pressure at the dicrotic notch.
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Discussion
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It is obvious that the marked difference in the ascending aortic
systolic
pressure waveform and upper limb pressure waveform is one of
the
major causes of the underestimation of vasodilator effects of
nitroglycerin
by upper limb blood pressure
measurements. Although maximal
systolic pressure usually coincides with
the late systolic peak
in the ascending aorta, it usually coincides
with the first
systolic peak in the radial artery. Since
nitroglycerin reduces
late systolic pressure in the
ascending aorta by reducing the
reflection wave,
6 the
reduction in the second systolic peak
is the same as the reduction in
maximal systolic pressure in
the ascending aorta. However, in the
brachial and radial arteries,
this reduction, even when marked, does
not appear as a reduction
in maximal systolic pressure because the
second systolic peak
occurs between the first systolic peak (maximal
systolic pressure)
and diastolic pressure. We can easily
recognize such differences
of pressure waveforms when we record
each pulse. Recently developed
arterial
tonometry
4 7 provides us with stable and accurate
pressure
waveforms. However, it is not easy to detect the early
and late
systolic shoulders, especially when the shoulder fails
to show a
distinct inflection point. Murgo et al
5 were the
first to
describe the concept of the augmentation index, which
they referred to
as the reflection return point in the ascending
aorta. Kelly et
al
4 introduced the term augmentation index.
The
augmentation index we used was the ratio of the height of
the late
systolic shoulder/peak to the early systolic shoulder/peak
in the
pulse, which was simpler than that in previous reports
but essentially
the same. Kelly et al
4 pointed out that a means
for
objective recognition of the early systolic shoulder was
needed. They
determined the early systolic inflection point
using the fourth
derivative wave of the second zero crossing,
which coincides with peak
flow velocity. This is very useful
for detection of the early systolic
shoulder, but for analysis
of the upper limb pulse waveform it
is necessary to clarify
the late systolic shoulder, and for this it is
important to
know where the late systolic inflection point is. The
fourth
derivative wave has four major segments, and the third zero
crossing
from below to above the fourth derivative indicates the late
systolic
inflection point. We developed the automatic detection of the
late
systolic shoulder using the third zero crossing from below to
above
the fourth derivative wave, which corresponds to the late
systolic
shoulder. The limitation of this method is the lower frequency
response
of 8.16 Hz, which is not used in the determination of the
maximal
pressure rise of the wave, such as maximal dP/dt. Gain loss
occurs
with the lower frequency derivative method. However, automatic
analysis
of pressure waveforms requires stable waveforms. The
major characteristics
of the radial pulse are included within 4 to 5
Hz,
8 whereas
the dicrotic notch contour can be
characterized within 8 Hz.
The frequency response (8.16 Hz) of this
system was considered
to keep the characteristic frequencies of radial
pulse and maintain
the dicrotic notch while eliminating the increased
signal-to-noise
ratio at higher frequencies. Recently, frequency
analyses of
upper limb pressure waves for determination of the
ascending
aortic pressure wave have been developed by Karamanoglu et
al
8 as a transfer function method, which is one of the
best estimates
based on wave analysis. However, it is possible
to compare the
ascending aortic pressure waveform and the upper limb
pressure
waveform in a time-domain relationship. This may be the one
approach
for exploring the importance of the recognition of the two
systolic
components and contributing to the understanding of not only
the
discrepancies between ascending aortic pressure and upper limb
pressure
but also the effects of vasodilators on lowering ascending
aortic
systolic pressure with the use of measurement of the reduction
in
the second systolic component in the radial artery.
Received January 31, 1995;
first decision February 21, 1995;
accepted March 30, 1995.
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References
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