Download Carotid arterial haemodynamics after mild degrees of lower

Clinical Science (1992) 83, 535-s-iO (Printed in Great Britain)
535
Carotid arterial haemodynamics after mild degrees of
lower-body negative pressure in man
P. J. LACOLLEY, B. M. PANNIER, M. A. SLAMA, J. L. CUCHE, A. P. G. HOEKS, S. LAURENT,
G. M. LONDON and M. E. SAFAR
Department of Internal Medicine, Hypertension Research Centre and INSERM (U 337), 8roussais
Hospital, Paris, France
(Received 3 Februaryj26 May 1992; accepted 16 June 1992)
1. Pulsatile changes in the diamettlr of the common
carotid artery were studied transcutaneously using an
echo-tracking technique in 15 normal subjects: eight
subjects b,fote and during application of graded
lower-bodyntlgative prtlSsurefrom - 5 to -15
mmHg, and seven subjects before and during weightbearing hea.d-up tilt at 30 and 60 degrees.
2. In concomitant studies of changes. in forearm
vascular resistance, it was seen that mild lower-body
negative pressure produced deactivathm of cardiopulmonary receptors without changes in systemic
blood pressure or heart rate.
3. After lower-body negative pressure, a significant
decrease in carotid arterial diastolic diameter [from
0.662tO.028 to 0.624tO.033cm (lower-body negative prtlSsure -10mmHg) and 0.640t 0.030em lowerbody negative pressure -15 mmHg), P< 0.001 and
< 0.05] was obstlrvoo.
4. After head-up tilt, carotid arterial diameter was
also significantly decreased at 30 and 60 degrees,
where.as a significa.nt increase il1 heart rate occll....ed
only at 60 degrees and mean blood pressure did not
change.
5. 'the study provides evidenee that the geometry of
the arterial wall is substantially modified by noninvasivemanoeuvrtlS such ashtlad-up tilting .and
lower-body ntlgative pressure. The latttlr is assumed
to selectively deactivate human cardiopulmonary
recepto.rs, but the present data suggest that local
chapges may also intlutlnctl carotid baroreceptors.
INTRODUCTION
Lower-body negative pressure (LBNP) is widely
used to study the role of cardiopulmonary receptors
in the low-pressure system in humans [1-3]. Graded
LBNP from -5 to -20mmHg produces a progressive decrease in central blood volume and
central venous pressure and an increase in forearm
vascular resistance in the absence of significant
changes in systemic blood pressure (BP) and heart
rate. In this situation, it is considered that there is
no activation of baroreeeptors in the high-pressure
system. However, with LBNP exceeding -20mmHg,
the heart rate increases and BP tends to decrease,
indicating that this degree of LBNP inhibits both
cardiopulmonary and arterial baroreeeptors.. Finally,
the basic premise is thought to be that a change in
systemic BPis the principal stimulus producing
stretch in arterial baroreoeptors,
Many experimental studies on high-pressure
system baroreeeptors have shown that the reflex
stimulus is the deformation of the arterial wall
rather than the level of BP [1-3]. With the application of LBNP, only changes in systemic BPplay
a part in the activation of baroreceptors, assuming a
passive response of the carotid artery to changes in
the BP distending the vessel. However, recent studies in man have Shown that these arteries do not
simply behave passively [4, 5], but, rather,respond
actively to neurohumoral stimuli, in particular to
those arising from baroreceptors in the low- and the
high-pressure systems [5]. In this regard, Ultrasonic
echo-tracking techniques have been developed in the
last few years for the transcutaneous evaluation of
the geometry of large arterial vessels [6-10]. The
most suitable artery for investigation is the common
carotid artery, a superficial and straight large artery,
in which it is possible to satisfactorily evaluate
deformation of the arterial wall, very close to the
carotid baroreceptors [6-lOJ.
The purpose of the present study was to determine changes in carotid arterial diameter after
LBNP and head-up tilting, two manoeuvres which
cause changes in the activation of mechanoreceptors
in the low-pressure system.
METHODS
Subjects
Fifteen normal male subjects Were included in the
study. They were aged between 22 and 39 years.
Their mean age was 29 ± 7 years (± SD) and their
height and weight Were respectively 173± 7emand
65±7 kg. BPwas measured with a mercury
key W!lrds: baroreflex mechanisms. common carotid artery, echo-tracking techniques, lower-body negative pressure•. tilting.
Abbreviations: BP, blood pressure, LBNP, lower-body negative pressure.
C!ltrespondence: Professor Michel Safar. Medecine Interne (M I), Hopital Broussais, 96 rue Didot, 75014 Paris. France.
536
P. J. Lacolley et al.
sphygmomanometer with the subjects in the supine
position after 15min of rest. The BP was measured
on 3 separate days before the haemodynamic study.
The systolic BP was consistently less than
140mmHg and the diastolic BP was less than
90 mmHg. Cardiovascular status (on physical examination), chest X-ray and electrokymograph were
normal in all subjects. The sodium intake was taken
to be between 60 and 120mmo1/24h, as measured
by 24h excretion. The study was approved by the
CNES (Centre National &Etudes Spatiales, Paris)
and by the Ethics Committee of INSERM (Institut
National de la Santk et de la Recherche Mtdicale,
Paris). All subjects freely consented to the investigation after a detailed description of the procedure
had been given. Subject familiarization included
tours of the laboratory and Clinical Research
Centre before entry into the study.
The haemodynamic study was performed during 1
day of hospitalization in a room with a controlled
temperature (21°C). The investigation began at
08.00 hours after a standard breakfast, with the
subject in the supine position. Mean, systolic and
diastolic BPs and heart rate were measured automatically in the left arm every 2min during each
period of the investigation, with a Dinamap Type
845 oscillometric BP recorder [S]. After 20min rest
in the supine position, haemodynamic determinations were performed up to 10.30 hours. Forearm
and carotid haemodynamic responses were studied
before and after the following two different
manoeuvres: in eight subjects, application of LBNP,
and in seven subjects the effect of head-up tilting
from the supine position. Samples for the determination of plasma catecholamine and dopamine
levels were taken before and after the application of
LBNP and were analysed as described by Cuche et
al. [ll]. A small catheter was inserted into an
antecubital vein at 08.00 hours, about 30 min before
the first blood sample was taken.
Determination of forearm haemodynamics
Forearm blood flow was determined in the supine
position by venous occlusion plethysmography
using a mercury strain gauge plethysmograph as
described previously [123. The forearm was placed
in 90" adduction, 5-10cm above the heart level. An
adjustable arm rest ensured that the forearm
remained in the same position relative to the heart.
A mercury strain gauge was applied to the arm 6cm
distal to the lateral epicondyle of the humerus and
was then calibrated. The position of the gauge was
marked with a reference mark. A pneumatic cuff
was placed around the arm for venous occlusion.
For the determination of blood flow, wrist occlusion
was used and venous occlusion was achieved by
cuff inflation to 50mmHg at a constant rate of
5 mmHg/s. Several consecutive flow curves were
recorded every 30s, the mean value being taken as
characteristic for each subject. Forearm vascular
0.0 J,
0
I
1
3
4
5
Time (s)
Fig. 1. Example of the displacement waveform of the anterior and
posterior walls of the common carotid artery. The lower part
represents the pulsatile change at each beat (6).
resistance was calculated as the ratio of mean
arterial BP to forearm blood flow. Reproducibility
and normal values for forearm vascular resistance
have been published in detail elsewhere [l2].
Carotid arterial parameters
Wall movement of the right common carotid
artery was measured using an original pulsed ultrasound echo-tracking system based on the principle
of Doppler shift. Two conditions were studied
before and during application of LBNP, and before
and during a tilt test. The details of the method
have been given elsewhere [7]. Briefly, this transcutaneous method allows the assessment of the
displacement of arterial walls during the cardiac
cycle and, hence, time-dependent changes in arterial
diameter relative to initial diameter at the start of
the cardiac cycle.
Based on the two-dimensional B-mode image, a
M-line perpendicular to the artery was selected
exactly lcm below the carotid bifurcation. The
radio-frequency signal of 4-8 cardiac cycles was
recorded, digitized and temporarily stored in the
computer memory. Two sample volumes, selected
under cursor control, were positioned on the anterior and posterior arterial walls. To avoid the possibility that nearby structures producing prominent
echoes might temporarily encroach on the selected
sample volumes, thus obscuring the vessel wall
signal, a system was developed which allowed the
sample volumes to track the vessel walls. The
displacement of the arterial wall was then determined by processing the Doppler signals originating
from the two selected sample volumes. This procedure gives high spatial resolution ( < 30 pm for
internal diameter and l p m for pulsatile change). A
typical displacement waveform of the anterior and
posterior walls of the common carotid artery is
shown in Fig. 1: the five successive values of the
stroke change in diameter during systole (D,-Dd),
the end-diastolic diameter (Dd) and the relative
stroke change in diameter [(D,- Dd)/Dd] were computed from the recording; however, only mean
Carotid haemdynamics afrer lower-body negative pressure
0.9
1
I
10
I
1
1
1
I
20
30
40
50
60
Time (min)
Fig.2. Carotid arterial diastolic diameter (D,,) during a Mmin
observation period in five subjects. Measurements were made by the
537
level of the antero-superior iliac crests. After a rest
period of 15min, the baseline recording was performed. The pressure within the box was then
reduced to levels of -5, -10 and -15mmHg by
using a domestic vacuum cleaner. These three levels
of negative pressure are known to not affect BP or
heart rate and therefore to ‘selectively’ deactivate
cardiopulmonary receptors, whereas a greater negative pressure (-40mmHg) is known to reduce
systemic BP and to involve arterial baroreceptors in
the reflex response [l]. Each stimulus of - 5 , -10
and -15mmHg was maintained for 5min in a
stepwise fashion. BP, heart rate, carotid arterial
parameters, forearm blood flow and vascular resistance were measured before and during each - 5 ,
- 10 and - 15mmHg stimulus. Arterial parameters
were measured at the third minute. Blood sampling
was carried out before LBNP and at the end of the
- 15mmHg stimulus period.
same observer.
Response to tilt test
values were considered for the purposes of the
present study.
The side on which measurements were made did
not influence the arterial dimensions. Indeed, in 17
other normotensive subjects (not included in the
present study), no significant difference was
observed between measurements performed on the
left and the right common carotid artery C7.0f1.0
versus 7.0 f0.8 mm, 0.45 f 0.12 versus 0.44 f0.09 mm
and 6.6f2.2 versus 6.4f 1.5% for D,, D,-D, and
(D,-Dd)/Dd, respectively]. Thus all arterial dimensional data given in the present study were from the
right common carotid artery.
The reproducibility of the method was studied in
five normotensive subjects. The coefficient of variation (SD expressed as a percentage of the mean of
several successive measurements) was used for this
purpose. Reproducibility was first assessed during
the recording of 4-8 successive cardiac cycles. The
mean coefficient of variation determined under these
conditions was 1f0.6 and 6+2% for Dd and
D,-D,, respectively. Secondly, reproducibility was
assessed during 12 measurements performed by each
of two observers during a 90min period in the same
five subjects. Under these conditions, the mean
intra-observer coefficient of variation was 3 f 1
(Fig. 2) and 8 f1% for D , and D,- D,, respectively.
The inter-observer reproducibility was 5 f 2 and
9 f 2% for D , and D, -D,, respectively. The reproducibility of all these parameters has been published
in detail elsewhere [13].
Response to LBNP
To achieve deactivation of cardiopulmonary
receptors, the eight subjects were placed in the
ne position, with their legs and lower abdomen
osed in a polyvinyl chloride box sealed at the
In seven subjects, BP, heart rate and carotid
parameters were measured with the subject in the
supine position and during 3 and 5min of 30 and
60 degrees, weight-bearing, head-up tilt. Particular
care was taken to ensure accurate BP determinations by keeping the subject’s arm exten
that the pressure device and tubing were con
at atrial level. All tilt tests were performed at least
twice with a 5min interval between tests. The first
tilt was performed to provide a period of familiarization before the second tilt, during which the
determinations were made. The BP response to the
first tilt was not significantly different from that
observed in response to the second tilt.
Statistical evaluation [141
Results were expressed as means f SD. A two-way
repeated analysis of variance test was performed on
the haemodynamic changes after LBNP. A P value
of less than 0.05 was considered significant.
RESULTS
Table 1 shows that there was no significant
change in heart rate, mean arterial, systolic and
diastolic BP and consequently pulse pressure during
LBNP. Forearm vascular resistance increased significantly (P<O.Ol).
During LBNP, carotid arterial diastolic diameter
decreased significantly (P<0.01) (Fig. 3). The
percentage change in pulsatile diameter was unaltered. No significant correlation was observed
between the changes in forearm vascular resistance
or between BP and the changes in carotid arterial
diastolic diameter.
Plasma catecholamine and dopamine levels did
not change after LBNP at - 15mmHg. Adrenaline,
noradrenaline and dopamine levels were, respecti-
P. J. Lacolley et al.
538
Table 1. Haemodynamic changes after LBNP. Values are means fSD. Statistical significance: *P <O.OS, **P <0.01, ***P <0.001
versus baseline. Abbreviations: SABP, systolic arterial B P DABP, diastolic arterial B P MABP, mean arterial B P HR, heart rate; FBF,
forearm blood flow; FR, forearm vascular resistance; D, carotid arterial diastolic diameter; D,, carotid relative stroke change in
diameter; NS. not significant.
Baseline
116+9
65f7
82+7
62+8
7.62+ 3.05
12.8f6.2
0.662f0.028
8.48f2.3I
SABP (mmHg)
DABP (mmHg)
MABP (mmHg)
HR (beatslmin)
FBF (ml min-1 IW-lml)
FR (mmHg ml-lmin 100-lml)
D (cml
D, (%I
**
0.70
F value
LBNP
- IOmmHg
-5mmHg
113k9
62f 19
80f9
62f9
5.25 f2.52***
18.2f lo***
0.638 0.028*
8.39 f3.06
+
I14+ 10
64+10
78+ 10
63+9
5.22 f2.33***
19*OfII**
0.624 f0.033***
8.25 f 2.06
- 15mmHg
I12f I2
61+10
79f I2
64f 10
4.78 I.64***
20.5f 10.6***
0.640 0.030*
8.21 2.43
+
+
+
NS
NS
NS
NS
0.00I
0.001
0.01
NS
x
E
3
8
Y
L
.-5 0.65
W
.s
s
4 0.70 .5
=
._
-u 0.65 -
c-
.-R
",0.60 -
U
0
s
Y
0.60
L
s
E 0.55 -
E
Y
K
g
Y
U
0.55
Baseline
-5mmHg
" 0.50 4
-1OmmHg
Baseline
-1SmmHg
J
Y
Fig. 3. Carotid arterial diastolic diameter after LBNP in eight
subjects. The heavy line and bars represent mean values. Statistical
significance: *P<0.05, **P <0.001 compared with baseline.
Table 2 Haemodynamic changes after tilting. Values are means+so.
Statistical significance: *P<0.05, **P<O.OI, ***P<O.001 versus baseline.
Abbreviations: SABP, systolic arterial BP; DABP. diastolic arterial BP;
MABP, mean arterial B P HR, heart rate; D, carotid arterial diastolic
diameter; D,, carotid relative stroke change in diameter; NS, not
significant.
Tilting
30 degrees
SABP (mmHg)
DABP (mmHg)
MABP (mmHg)
HR (beatslmin)
D (cm)
D" (%)
120+8
68+5
85+5
62+6
0.664k0.033
8.03 2.02
+
118+7
69k6
86+5
62+5
0.631 L-0.042
7.61 1.56
+
F value
60 denrees
118+7
'
30 degrees
60 degrees
Tilting
LBNP
Baseline
-
70+7
86+7
69+3
0.624+0.053
7.29f 1.64
NS
NS
NS
<0.002
<0.01
NS
vely, 45 +40, 164+ 55 and 33 f45 pg/ml before and
37f25, 161f98 and 29+3Opg/ml after LBNP at
- 15mmHg.
BP did not change during the 30 and 60 degrees
tilt tests. Heart rate increased significantly
(P<O.OOl) only at 60 degrees (Table 2). Table 2
Fig. 4. Carotid arterial diastolic diameter after tilting in seven
subjects. The heavy line and bars represent mean values. Statistical
significance: *P<0.05, **P<O.Ol compared with baseline.
shows that the carotid arterial diastolic diameter
decreased significantly (P<0.01) (Fig. 4) at 30 and
60 degrees without any alteration in the percentage
change in diameter.
DISCUSS10N
LBNP is a widely accepted method used to
achieve selective deactivation of cardiopulmonary
receptors of the low-pressure system in humans 11,
15-18]. Zoller et aZ. [19] have shown that, with
LBNP levels of - 5 and - lOmmHg, central venous
pressure decreased and forearm vascular resistance
increased in the absence of significant changes in
mean arterial BP, arterial pulse pressure and heart
rate. A beat-to-beat analysis of systemic arterial BP
recorded at high gain did not show any transient
decrease in systolic BP that might have inhibited
arterial baroreceptors. In contrast, significant
changes in BP and heart rate occur when LBNP is
applied at levels more negative than -20mmHg,
which therefore simulate passive tilting [l, 15-18].
Carotid haemdynamics after lower-body negative pressure
Such studies, including the present one, might suggest that mild LBNP is a safe method with which to
investigate the role of cardiopulmonary receptors
alone in humans. However, previous studies have
not evaluated the changes in the geometry of the
carotid artery after LBNP.
In recent years, several devices have been utilized
to measure arterial diameter and wall motion transcutaneously by tracking echo signals from both the
anterior and posterior arterial walls [&lo]. Earlier
models [6] used an amplitude tracking method,
which had several drawbacks. Superimposed echoes
from the tissue surrounding the artery, as well as
imperfect alignment of the ultrasonic beam perpendicular to the arterial wall, caused significant and
unpredictable amplitude changes in the echo waveform. Newer devices have a high spatial resolution
with a better linearity, dynamic range and tracking
speed, even in the presence of a low original signalto-noise ratio. The present apparatus was substantially improved by the additional use of measurement of the Doppler shift, thus allowing a high
degree of reproducibility to be achieved [7]. Indeed,
during LBNP or tilt testing one can be certain that
the point of measurement in the vessel is not
dislocated in the longitudinal and transverse directions, and repeated evaluations of two-dimensional
B-made imaging are required for this. In the present
work, this possibility of dislocation does not fit with
our two principal results after LBNP and tilting at
the site of the common carotid artery, lcm just
below the carotid bifurcation: a decrease in carotid
arterial diastolic diameter, but no alteration in the
ge change in pulsatile diameter.
r LBNP and tilting, we did not find any
modification of the percentage change in pulsatile
arterial diameter. Since brachial pressure was also
found to be unchanged, it can be suggested that no
significant modification of carotid arterial distensibility occurred [20, 211. However, this possibility
should be considered very cautiously. First, a slight
tendency towards a reduced pulse pressure when
measured indirectly was noted, and it may be that
lower negative suction might have modestly reduced
stroke volume [16], which would per se slightly
reduce the pulsatile diameter changes. Secondly, the
oscillometric apparatus used (Dinamap) is optimized
for mean arterial BP measurements and may be less
reliable for systolic and diastolic BP. Thirdly, pulse
pressure difYers physiologically at the site of the
carotid and the brachial arteries, due to the amplification of pressure pulse from central to peripheral
arteries [20], and pressure wave transmission may
have been modified after LBNP or tilting. For all
these reasons, the present commehts will be focused
exclusively on the substantial changes in the geometry of the arterial wall that we observed, namely
a significant decrease in carotid arterial diastolic
diameter. In other words, the dominant finding of
this study was that mild LBNP and head-up tilting
were associated with a lower degree of stretch of the
539
carotid arterial wall, due to a reduction in vessel
diameter without any change in mean systemic BP.
At this point, it should be stressed that the
mechanism of the decrease in arterial diameter may
differ after LBNP or tilting. In the latter case, the
intra-carotid BP will change due to a hydrostatic
pressure difference from the atrial reference level [1,
2, 201. In contrast, after LBNP, the role of passive
modification in arterial diameter caused by BP
changes may be excluded, suggesting several other
hypotheses.
Deactivation of cardiopulmonary receptors has
recently been shown to be associated not only with
an increase in forearm vascular resistance (i.e.
arteriolo-constriction), but also with a reduction in
brachial artery diameter [5]. Reduction in brachial
artery diameter has been shown to be due either to
neurogenic factors or to a flow-dependent mechanism [5]. It is thus possible that deactivation of
cardiopulmonary receptors may also be associated
with a reduction in carotid arterial diameter. There
are, however, several arguments against this hypothesis. First, cardiopulmonary baroreceptor mechanisms have a predominant role in skeletal muscle
(as in the forearm) and no reports of an effect on
the large arteries exist, particularly at the site of the
carotid circulation [l]. Secondly, in our study, there
was no correlation between changes in forearm
vascular resistance and changes in carotid arterial
diastolic diameter. On the other hand, humoral
changes associated with decreased cardiopulmonary
blood volume and filling pressure of the heart after
LBNP might also contribute to the constriction of
the carotid artery. However, LBNP at levels of -5,
-10 and -15mmHg is known to produce little
change in plasma renin activity and plasma vasopressin concentration [11 and no substantial modification of plasma catecholamine or dopamine levels
occurred in the present study, as in others [l].
The method of applying LBNP itself might contribute to the carotid response observed. During
LBNP a subatmospheric pressure is applied to
vessels and viscera in the pelvis and abd
possibility that reflexes originating in sen
tors in these areas may contribute to circulatory
and humoral modifications during LBNP must be
taken into account [l]. Another possibility is that
mild LBNP produces slight changes in cardiac
output with resulting changes in arterial diameter
through the mechanism of flow-dilatation (or constriction) [22]. Howeve
rmacologically induced
changes in carotid bl
shown to be unusually associated with concomitant
changes in carotid arterial diameter [23]. The last
hypothesis is that positional manoeuvres causing a
change in cardiopulmonary blood volume and filling pressure might modify per se the size of the
heart and vessels [24], resulting in a change in the
longitudinal stretch of the carotid artery. Our findings of decreased carotid arterial diameter after tilt
might partly favour this possibility. With this pro-
540
P. 1. Larnlley et al.
cedure, a decrease in carotid arterial diameter was
already observed at 30 degrees of tilt, before any
increase in heart rate was observed. At 60 degrees of
tilt, heart rate increased, indicating a significant
activation of baroreceptors in the high-pressure
system.
At the end of this discussion, it is important to
notice the complexity of the physiological situation,
as results from the classical analysis of the baroreflex mechanisms [2]. The arterial baroreceptors
contain both adventitial stretch receptors with myeh a t e d afferents, functioning as if coupled ‘in parallel’ with other wall elements (being thus unloaded
by arterial constriction), and unmyelinated stretch
afferents more or less infiltrating the media (as if
coupled ‘in series’ with the muscle cells) which may
rather become activated during reflex constriction of
the carotid artery. Thus, these two sets of bar0
(stretch) afferents might tend to balance each other
out with respect to their potential secondary contribution to the overall reflex effects of volume receptor unloading.
In conclusion, the present study has shown that,
with graded application of mild LBNP, deactivation
of cardiopulmonary receptors is associated with a
significant reduction in carotid arterial diameter,
lcm below the carotid bulb. The possibility that
this phenomenon could produce a lower level of
stretch at the site of arterial carotid receptors
should be considered as a factor which might affect
the habitual interpretation of interactions between
baroreceptors in the high- and low-pressure systems
in humans. Further studies are needed on this
important problem.
3.
4.
5.
6.
7.
8.
9.
10.
II.
12.
13.
14.
15.
16.
17.
ACKNOWLEDGMENTS
This study was performed with the aid of grants
from the Institut National de la SantC et de la
Recherche Midicale (INSERM-U337), the Centre
National &Etudes Spatiales (CNES), Dassault
Electronique (B. Daugny) and the Comit6 de
Recherche Clinique de l’Assistance Publique, Paris.
We thank Mrs Sylvie Minne for her excellent
technical assistance.
18.
19.
20.
21.
22.
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