Download Heart rate control of blood pressure variability in

Clinical Science (1998) 95, 33–42 (Printed in Great Britain)
Heart rate control of blood pressure variability
in children: a study in subjects with fixed
ventricular pacemaker rhythm
Isabelle CONSTANT, Elizabeth VILLAIN*, Dominique LAUDE†, Arlette GIRARD†,
Isabelle MURAT and Jean-Luc ELGHOZI†
Service d’Anesthe! sie Re! animation Pe! diatrique, Ho# pital d’enfants Armand Trousseau, 26 Av. du Dr Arnold Netter, 75571 Paris,
France, *Service de Cardiologie Pe! diatrique, Ho# pital Necker-Enfants Malades, Paris, France, and †Centre de Pharmacologie
Clinique, Association Claude Bernard, CNRS URA 1482, Ho# pital Necker-Enfants Malades, Paris, France
1.
To investigate the influence of heart rate variability on blood pressure variability, short-term variability in heart rate and blood pressure was studied in 10 children with fixed ventricular pacemaker
rhythm (80 beats/min). Ten healthy children, in sinus rhythm, served as a reference population.
2.
Arterial blood pressure and heart rate were measured continuously using a finger arterial device
and an ECG respectively. Power spectra for heart rate and blood pressure (systolic and diastolic)
were calculated in both supine and orthostatic positions. In addition, acute changes in blood
pressure and heart rate during active standing were studied.
3.
Healthy children exhibited considerable heart rate variability, which was slightly more
pronounced in the supine position, while children with a fixed ventricular rate had no heart rate
variability in either position.
4.
Despite the differences in heart rate variability, mean systolic blood pressure and its variability
profiles were poorly affected by the suppression of heart rate variability. The lack of autonomic
control on the sinus node was associated with a reduction in magnitude of the changes in systolic
blood pressure variability induced by orthostatic posture.
5.
The suppression of heart rate fluctuations induced a noticeable decrease in diastolic blood
pressure fluctuations, which was most conspicuous in the children with fixed cardiac rhythm
when in the supine position. This may be explained by the lack of diastolic blood pressure
fluctuations, physiologically due to heart rate fluctuations through the run-off effect : the longer
the cardiac cycle, the greater the diastolic pressure decay. These results may challenge the classical
theory of baroreflex-mediated diastolic blood pressure control described in adult patients.
6.
During active standing, the early drop in systolic blood pressure was greater in subjects with
fixed ventricular rhythm. A rise in heart rate of 36 beats/min was observed in the healthy
subjects in response to active standing.
7.
We conclude that in normal children, heart rate fluctuations increase the blood pressure
variability rather than buffering it. However, during acute orthostatic stress, the abrupt
baroreflex-mediated heart rate rise may partly compensate for the reduction in blood pressure.
Key words : autonomic nervous system, blood pressure, children, heart rate, pacemaker, respiratory sinus arrhythmia.
Abbreviations : BP, blood pressure ; DBP, diastolic blood pressure ; HF, high frequency ; HR, heart rate ; MF, mid frequency ;
PM, pacemaker ; SBP, systolic blood pressure.
Correspondence : Dr Isabelle Constant.
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I. Constant and others
INTRODUCTION
The regulation of blood pressure (BP) is complex.
Mechanical factors such as respiration synchronous
fluctuations in stroke volume, neurohormonal influences
such as those of the renin–angiotensin system or sympathetic nervous system and acute stress such as sudden
active standing, contribute to beat-to-beat variability of
BP in humans. Since heart rate (HR) is a determinant of
stroke volume and of cardiac output, it plays a major role
in BP regulation. The modulatory influence of HR,
driven by the autonomic nervous system, is in turn
regulated by the arterial baroreflex [1].
Spectral analysis of continuous measurements of BP
and HR provides information about the relationship
between HR and BP variabilities. Heart rate variability
may interact with BP variability in two ways : on one
hand it may have a feedforward effect on BP variability,
and the loss of HR variability may lead to a decrease in
BP variability. On the other hand, HR variability may
have an anti-oscillatory role in BP regulation (feedback
effect) through the conventional baroreflex mechanism,
and the loss of HR variability may increase BP variability.
In addition, it has been suggested that the influence of
HR fluctuations on BP variability depends in part on the
body’s position, as demonstrated for respiratory sinus
arrhythmia and respiratory systolic blood pressure (SBP)
oscillations [2].
The most obvious way to elucidate the relationship
between BP and HR is to study BP variability profiles
when HR does not fluctuate. Withdrawal of HR oscillations can be obtained by pharmacological blockade but
this procedure may modify the physiological relationship
between HR and BP. This relation may also be analysed
in patients with fixed ventricular pacemaker rhythm, but
most of these patients suffer from cardiovascular disease
that may impair the normal interaction between HR and
BP [3]. To avoid this bias, we studied young subjects with
normal cardiac performance, in whom a pacemaker was
implanted for congenital impairment of atrioventricular
conduction. These paced subjects with fixed ventricular
rhythm were compared with age-matched healthy subjects, in whom the physiological HR variability is usually
very pronounced, in order to evaluate the results of the
withdrawal of HR fluctuations on short-term BP regulation.
Systolic and diastolic BP were measured using a noninvasive finger BP device. Heart rate was derived from
the R-wave of the ECG. These parameters were subjected
to spectral analysis as described previously [4]. The study
was performed in both the supine and orthostatic
positions to characterize the sympathetic and vagal
contributions to the relationship between BP and HR. In
addition, changes in BP and HR during standing were
studied in order to evaluate the results of the lack of
# 1998 The Biochemical Society and the Medical Research Society
baroreflex-mediated HR response during acute physiological stress.
METHODS
Study population
Results from 10 children with an implanted bipolar
DDD pacemaker [age 8.7³2.2 (6–13) years, weight
27.6³10.8 kg] and 10 healthy children with sinus rhythm
[age 8.6³2.5 (6–13.5) years, weight 28.8³6.0 kg] form
the basis of this report. The indication for pacemaker
implantation was isolated congenital complete heart
block. All paced children had normal cardiac anatomy
and left ventricular function as assessed by echocardiography. None of the patients was taking medication. One hour before recordings, the paced children
(PM group) were programmed to the VVI mode at a
pacing rate of 80 beats}min.
Study protocol
Children were studied in the morning in a quiet room
at 22 °C. Electrocardiograph measurements were taken
with disposable electrodes attached to the thorax, placed
to provide clear R-waves, and connected to a Datex
cardiocap II monitor (Instrumentation Corp., Helsinski,
Finland). Finger arterial pressure was monitored noninvasively by a Finapres device (model 2300 ; Ohmeda,
Trappes, France). In this study, all children had a finger
circumference of between 42 and 60 mm. To ensure an
optimal Finapres BP measurement we used appropriate
cuff sizes (S or M) according to the manufacturer’s
instructions. The cuff was fitted to the third finger of the
right hand, which was passively maintained at heart level
during the manoeuvres. Three recordings were obtained :
the first during 5 min in the supine position after a 10min rest, the second during the acute change from the
supine to standing position, and the third, of 5 min
duration, when the subjects were in orthostatic posture,
3 min after active standing.
Breathing was quantified by respiratory inductance
plethysmography with a Respitrace device (Ardley, New
York, U.S.A.). During recordings obtained in the supine
and standing positions, children breathed spontaneously
during the first minute and were then asked to control
their breathing frequency using an auditory signal from
an electronic metronome. The controlled respiratory rate
was determined from the spontaneous breathing rate of
each child during the first minute of recording. All HR
and BP variability studies were performed during controlled breathing.
The investigation conformed to the principles outlined
in the Declaration of Helsinki. The nature of the research
was explained to the parents and informed consent was
obtained.
Heart rate control of blood pressure in children
Table 1 Average SBP, DBP and HR values in the supine and standing positions obtained in
paced children (group PM) and healthy controls (group C)
This table includes the standard deviations of SBP, DBP and HR time series. Data are means³S.E.M. Statistical significance :
*P ! 0.05, **P ! 0.01, ***P ! 0.001, group PM versus group C ; †P ! 0.05, ††P ! 0.01, †††P ! 0.001, standing
versus supine.
Supine
Group PM
Group C
Standing
Group PM
Group C
SBP
(mmHg)
S.D. SBP
(mmHg)
DBP
(mmHg)
S.D. DBP
(mmHg)
84.3³3.2
76.2³4.5
4.6³0.4
4.5³0.4
43.9³3.3
38.8³3.1
2.2³0.2**
3.0³0.2
94.8³2.9
99.8³6.2†††
4.6³0.4
5.7³0.6†
54.5³2.7††
62.6³4.3†††
2.7³0.1
3.0³0.2
Data processing and spectral analysis
The details of data sampling and analysis have already
been described [4]. The analogue output of the Datex
monitor and of the Finapres device was connected to an
analog-to-digital converter to permit data acquisition,
storage and analysis using a microcomputer. The BP and
ECG signals were digitized (500 Hz) and processed by an
algorithm based on feature extraction to detect and
measure the characteristics of a BP cycle and an R-wave
(Anapres 3.0, Notocord Systems, Croissy}Seine, France).
Systolic and diastolic blood pressure (DBP) were extracted from the BP signal, and HR was calculated as
60 000 divided by the heart period in milliseconds,
measured from the corresponding R-wave and the
preceding one. A sampling rate of 10 Hz was chosen
without interpolation, i.e. SBP, DBP and HR values were
replicated every 0.1 s until a new BP cycle or R-wave
occurred within a 0.1 s window.
The evenly spaced sampling allowed direct spectral
analysis using a fast-Fourier transformed (FFT) algorithm on a 2048-point stationary time series. This corresponded to a period of 3 min 25 s at our sampling rate.
Thus, each spectral band corresponded to a harmonic of
5}1024 Hz, or 0.00488 Hz. Power of the HR or BP
spectrum (ordinates) shown in the figures had units of
(beats}min)# or mmHg#. Modulus (square root of the
power) was used for calculations and statistical analysis.
The integration of the values of consecutive bands was
computed to estimate the various components of the
variability. As breathing frequency was controlled, the
high-frequency (HF) oscillation was easily detected
within the 0.2–0.5 Hz range, and we summed the value of
the bands corresponding to respiration and the four
values of higher and smaller frequency (i.e. nine values) to
integrate the HF components of SBP, DBP and HR. The
mid-frequency (MF) component was obtained by integration of the values of the consecutive bands from
0.0635 to 0.127 Hz of the SBP, DBP or HR spectrum, in
order to include the 10-s rhythm (0.1 Hz) [5]. We also
calculated descriptive statistics (means, S.D.) of the
HR
(beats/min)
80.2³0.0
84.5³4.2
80.3³0.1***
102.9³5.9††
S.D. HR
(beats/min)
0.1³0.0***
7.4³0.5
0.3³0.1***
6.4³0.4†
distribution of the variables (SBP, DBP and HR) for each
stationary period of 205 s used for spectral analysis.
Data obtained during active standing were analysed as
described by Lindqvist et al. [6]. The baseline values were
obtained by averaging SBP, DBP and HR over 10 s, 30 s
before the start of upright posture. The changes measured
during standing up included the initial BP rise, the BP
fall, the subsequent BP overshoot taken 20 s after the
initial rise of BP, and in each case the corresponding HR.
The early steady-state was also evaluated by averaging
the BP and the HR over 10 s at 1 and 3 min after the
initial BP rise. In addition, we calculated the BP values at
the maximal HR rise in the control group. These values
were compared with the BP values measured 12.8 s after
the initial rise in SBP in the PM group, which corresponds
to the average time interval from the initial SBP rise to the
maximal HR rise in healthy children.
Statistical analysis
Data are expressed as means³S.E.M. Significant differences between patient groups and postures were
determined by two-way analysis of variance for repeated
measures. A logarithmic transformation of the data was
performed before the comparisons when the variance
ratios of the different groups were significant. When the
F-value of the analysis of variance was significant,
differences between groups and postures were tested
using the modified t-statistics based on the Bonferroni
method. Differences were considered to be statistically
significant when the P value was less than 0.05.
RESULTS
Effect of suppression of HR variability in
physiological stationary conditions (supine
and standing)
Respiration
Breathing frequency was effectively controlled in all
subjects, with a similar spontaneous respiratory rate in
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I. Constant and others
# 1998 The Biochemical Society and the Medical Research Society
Heart rate control of blood pressure in children
Table 2 Average MF and HF components of the HR, SBP and DBP spectra (absolute and relative values) in supine and standing
positions obtained in paced children (group PM) and in healthy controls (group C)
Relative values were calculated as the contribution of each spectral component to the variance. Data are means³S.E.M. Statistical significance : *P ! 0.05,
**P ! 0.01, ***P ! 0.001, group PM versus group C ; †P ! 0.05, †††P ! 0.001, standing versus supine.
HR MF
(beats/min)
Supine
Group PM
Group C
Standing
Group PM
Group C
HR MF
(%)
HR HF
(beats/min)
HR HF
(%)
SBP MF
(mmHg)
SBP MF
(%)
SBP HF
(mmHg)
SBP HF
(%)
8³2
8³2
0.0³0.0*** 1³0***0.1³0.0*** 16³3
2.6³0.3
14³3 2.8³0.4
16³3
1.5³0.2 11³2
1.6³0.1 13³2
1.3³0.2
1.1³0.1
0.0³0.0*** 1³0***0.1³0.0*** 18³7
2.5³0.3
16³3 2.0³0.4
11³3
1.7³0.2 15³3
2.1³0.2† 15³3
1.3³0.2
9³2
1.8³0.2††† 11³3
the two groups. Mean values, in supine and standing
position respectively, were 21.5³0.9 and 21.7³
1.4 breaths}min in the PM group and 19.2³1 and
19.4³2 breaths}min in the healthy children.
Heart rate
In the supine position, the fixed HR of the PM group
was similar to that observed in the control group.
Standing position was associated with an increase in the
average HR in the control group (18.4³2.1 beats}min).
In the paced individuals HR was unresponsive to changes
in posture (Table 1).
Healthy children exhibited a high degree of HR
variability, as estimated by the S.D. of the distribution,
ranging between 4 and 10 beats}min. Frequency domain
analysis of this variability revealed classical components,
mainly assessed by the MF peak and the respiratory (HF)
peak of the power spectra (Figure 1 and Table 2). Overall
variability and HF peak were decreased in the upright
position.
As expected, in children with cardiac pacing, beat-tobeat variability was markedly reduced and power spectra
were dramatically flat (Figure 1, Table 2).
Blood pressure
The fixed HR did not affect average SBP and DBP
values (Table 1). In all children, standing position was
associated with higher levels of SBP and DBP compared
with the supine position. This postural effect was less
pronounced in the PM group for both SBP (­10.5³
3.9 mmHg versus ­23.6³2.9 mmHg, P ! 0.01) and
DBP (­10.6³4.5 mmHg versus ­23.8³1.6 mmHg, P
! 0.01). Despite the lack of HR fluctuations in children
with a fixed ventricular pacemaker rhythm, overall
variability and power spectra of SBP were similar in the
two groups (Table 2 and Figure 1) in the supine position.
Standing position was associated with an increase in MF
DBP MF
(mmHg)
DBP MF
(%)
0.8³0.1** 15³2
1.3³0.1
19³2
1.2³0.1†
1.4³0.1
DBP HF
(mmHg)
DBP HF
(%)
0.3³0.0** 2³1
0.7³0.1
6³2
23³4† 0.5³0.1** 4³2*
24³4 0.9³0.1
9³2
and HF components in the control group, while in the
PM group this postural effect was not significant.
In contrast, the DBP of the paced children displayed a
reduction in overall variability in the supine position.
This was associated with a decrease in the MF and HF
components of the power spectra when compared with
that of the control group. In response to upright posture
only the HF component was reduced (Figure 1 and Table
2).
Effect of suppression of HR variability
during acute physiological stress (active
standing)
These results are summarized in Table 3, and in Figure
2.
Heart rate
The programmed HR of the PM group and the average
resting HR of the control group were comparable. No
change in HR was detected in children with fixed
ventricular rhythm during active standing up. The characteristic HR acceleration upon standing was observed in
control subjects with an average maximum rise of
36.0³3.2 beats}min, followed by a deceleration leaving
the HR 15 beats}min above the baseline 1 min after
active standing up. The time interval calculated from the
initial SBP rise to the maximal HR increase in control
subjects was 12.8³0.9 s.
Blood pressure
Resting supine BP was similar in the two groups
examined. Both SBP and DBP increased in all children
during the first few seconds after the transition from the
supine to the standing position. The mean initial increase
in BP did not differ between groups (14.2³2.1}
10.0³2.4 mmHg in the PM group and 14.8³4.2}
10.0³3.1 mmHg in the control group). The subsequent
Figure 1 Examples of SBP, DBP, HR and respiration recordings from one 8-year-old healthy child (left) and one 8- year-old
child with a fixed ventricular rhythm (right) obtained in the supine position, with the corresponding power spectra
# 1998 The Biochemical Society and the Medical Research Society
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I. Constant and others
Figure 2 Effects of active standing (arrow) on SBP, DBP and HR in two 9-year-old children from the PM group (top) and the
control group (bottom)
reduction in SBP was significantly greater in the PM
group (22.9³4.0 mmHg) than in the control group
(9.5³3.1 mmHg). There was a tendency (not statistically
significant) for DBP to behave in a similar manner. The
overshoot of SBP and DBP was present in all children
and did not differ between the two groups. The early
steady-state level of BP after 1 and 3 min in the standing
position was also similar in the two groups.
# 1998 The Biochemical Society and the Medical Research Society
DISCUSSION
Young subjects, previously implanted with a cardiac
pacemaker for the alleviation of a congenital impairment
of atrioventricular conduction but with no other clinical
indications, provide a clinical model whereby the relationship between BP and HR can be assessed. In this
study we provided evidence documenting : (i) the absence
Heart rate control of blood pressure in children
Table 3 Effects of active standing on SBP and HR in paced children (group PM) and in healthy
controls (group C)
Overshoot of SBP was taken 20 s after the initial rise of SBP. Data are means³S.E.M. Statistical significance : *P ! 0.05,
***P ! 0.001, group PM versus group C.
Control
SBP (mmHg)
Group PM
Group C
HR (beats/min)
Group PM
Group C
82.9³1.9
81.8³4.4
80.2³0.0
83.9³4.4
Minimum SBP
SBP at max.
HR rise
60.0³3.2*
72.3³4.8
77.9³3.3
88.8³4.8
80.2³0.0*** 80.2³0.1***
109.9³4.2
120.6³4.8
of a pronounced effect of the lack of HR fluctuations on
SBP variability in steady posture, except for a reduction
in the magnitude of changes in SBP variability induced by
standing posture ; (ii) a noticeable reduction of DBP
variability in cardiac-paced subjects, indicating that in
healthy children changes in HR were the predominant
modulator of DBP ; and (iii) a larger drop in SBP during
standing up in children deprived of baroreflex-mediated
HR response.
The original feature of our population of healthy
children lies in the considerable HR variability, which is
spontaneously observed and more pronounced than that
observed in adults. It should be underlined that the
respiratory contribution to HR variability in healthy
children was comparable to the MF contribution in
supine and standing position, in contrast to the findings
described in adults [7]. These data reflect a high vagal
modulation of HR in children, whatever the posture.
Reliability of continuous BP measurements
For continuous BP measurement we used the noninvasive Finapres 2300 device. In adults, the accuracy of
the Finapres has been widely evaluated in steady-state
conditions and during active standing up using intraarterial pressure as the reference [6,8,9]. Triedman and
Saul [10] compared intra-arterial and continuous noninvasive BP measurements in paediatric patients in
intensive care. We recently compared finger and intraarterial BP measurements in children during anaesthesia
and during the recovery period [11]. Our results, in
agreement with those obtained by Triedman and Saul
[10], demonstrated reliable estimation of BP variability
profiles using the Finapres device, with a low intrapatient standard deviation of bias.
Effect of lack of HR variability in supine and
standing positions
The main components of SBP variability obtained in
physiological stationary conditions were similar in children with fixed ventricular rhythm and in healthy
Overshoot
Steady state,
1 min
Steady state,
3 min
96.7³3.9
102.7³3.2
95.1³4.4
97.3³4.2
94.7³5.1
99.6³4.8
80.2³0.1*** 80.2³0.1***
97.9³3.9
98³5.4
80.2³0.1***
102.2³6
children, despite the suppression of short-term HR
fluctuations in the former group. However, withdrawal
of the autonomic control on the sinus node was associated
with a blunted response to orthostatic posture.
The extent to which BP variability is linked to HR
variability is debatable. Heart rate oscillations mediated
by the arterial baroreflex may buffer BP variations [1,12]
whereas HR changes may induce variations in cardiac
output and BP. Cardiac pacing is associated with a
reduction in respiratory BP fluctuations in both dogs [13]
and in healthy human subjects [2], whereas in exercising
subjects atropine produces an increase in SBP variability
[1]. In contrast, after pharmacological intervention in
humans, Triedman and Saul [14] demonstrated that
changes in SBP were insensitive to autonomic cardiac
blockade and were therefore probably mediated by the
mechanical effects of intrathoracic pressure. Our results
are in accordance with the latter study.
The MF SBP oscillations are dependent on an intact
autonomic nervous system and may stem from a central
oscillator of sympathetic tone. High-frequency changes
in SBP proceed from changes in cardiac output, probably
via respiratory-induced changes in HR and ventricular
filling [15,16]. In the present study, the healthy children
showed the classical increase in MF and HF components
of SBP power spectra when shifting from a supine to a
standing position [17,18]. In contrast, the paced children
presented a dampened increase in the MF and HF SBP
components during the same change in posture. This
blunted orthostatic response has previously been observed after surgical cardiac denervation in cardiac
transplant patients [19], and after pharmacological blockade in healthy subjects in whom SBP variance was
decreased in the standing position [16]. Furthermore,
these findings agree with the blunted reflex increase in the
MF component of BP variability observed during nitroglycerine infusion in dogs with bilateral stellectomy
[18,20]. Together these results suggest that fluctuations of
HR may increase fluctuations of SBP rather than reduce
them. Our results confirm a noticeable effect of posture
on interactions between HR, respiration and BP [2,15].
# 1998 The Biochemical Society and the Medical Research Society
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I. Constant and others
Heart rate Systolic and diastolic
Respiration
(bpm)
arterial pressure
(arbitrary units)
(mmHg)
40
100
100
60
60
100
100
80
80
260
240
240
220
Figure 3
5 sec
Experimental records from one supine control subject (left) and one supine paced subject (right)
The healthy 7-year-old child exhibited DBP fluctuations in which each decrease occurred synchronously with the HR deceleration. In the paced 7-year-old child, the
lack of fluctuations of HR was associated with markedly reduced DBP changes. Furthermore, the periodic SBP decreases occur in both cases at the end of inspiration.
The orthostatic accentuation of SBP fluctuations observed in control subjects might be due to marked HR
variations resulting in cardiac output and subsequent BP
variations. These BP fluctuations may in turn initiate
baroreflex-mediated vasomotor oscillations. Moreover,
pressure fluctuations may be increased by the baroreflex
closed loop pressure–pressure. Changes in ventilation
pattern contribute to changes in the magnitude of
respiratory SBP fluctuations [21]. In our study, breathing
was monitored by respiratory inductance plethysmography, but the signal was not calibrated, thereby
preventing us from converting the amplitude of the
respiratory curve into volume, as required for calculation
of tidal volume. Although the respiratory rate was
comparable between the two groups, and within each
group in the two positions, we cannot fully eliminate
changes in respiratory volume as a mechanism contributing to the differences observed between the two
groups. As congenital heart block with normal cardiac
function is an uncommon pathology, a relatively low
number of subjects was included in our study. Hence the
possibility of the existence of a type II error cannot be
discounted.
Our results revealed that suppression of HR fluctuations through pacing unexpectedly reduced DBP variability. This interesting finding may be explained by the
lack of DBP fluctuations via the run-off effect (i.e. the
longer the cardiac cycle, the greater the diastolic pressure
decay) when the R–R interval is fixed. Cardiac cycle
length directly influences the amount of diastolic decay
and thus DBP. Suppression of HR variability would
therefore be expected to stabilize DBP. This mechanism
is illustrated in Figure 3 by the simultaneous fluctuations
of DBP and HR as occur in a healthy child, compared
with those in a paced child where the DBP fluctuations
# 1998 The Biochemical Society and the Medical Research Society
were markedly reduced because the R–R interval and
diastolic decay remained constant. These results are in
accordance with the decrease in magnitude of respiratory
modulation of DBP after cardiac autonomic blockade in
healthy adults with atropine and propranolol [14]. Our
findings contrast with the beat-to-beat model of the
cardiovascular system published by de Boer et al. [12].
They postulated that the HR is passively modulated by
BP fluctuations, over the baroreflex arc. An increase in
SBP due to respiratory effects induces a lengthening of
the R–R interval, and hence the diastolic run-off period ;
thus the diastolic respiratory fluctuations are much less
than the systolic respiratory fluctuations. Following this
hypothesis, suppression of the R–R interval’s ability to
vary should result in an increase in DBP variability. The
discrepancy between this model of adult cardiac function
and our present findings may result from the ample
vagally mediated respiratory sinus arrhythmia observed
in children. Indeed, our results suggest that respiratoryinduced HR fluctuations may overcome the fast baroreflex-mediated control of R–R interval. This effect could
be more evident in the supine position where parasympathetic tone is enhanced. Metronome controlled
breathing has been demonstrated to enhance respiratory
sinus arrythmia [18]. However, in our study, the metronome respiratory rate was chosen so that breathing
would be close to each subject’s spontaneous respiratory
rate and would not therefore influence the magnitude of
respiratory sinus arrythmia to any significant degree [22].
As DBP variability determines to a large extent the
sympathetic outflow via the arterial baroreflex mechanism [23], the dampening of DBP fluctuations may
affect SBP variability, especially in the upright position
where baroreflex mechanisms are activated. The dampening of SBP changes relating to orthostatic posture in the
Heart rate control of blood pressure in children
PM group compared with the healthy group is consistent
with this hypothesis.
Effect of lack of HR variability in acute
physiological stress
During active standing we demonstrated that the fall in
SBP was greater in children with a fixed ventricular rate
than in healthy children.
The initial circulatory responses upon rising have been
well described [24,25]. The mechanism underlying the
characteristic initial reduction in BP upon standing is
thought to be as a result of muscular vasodilatation
insufficiently matched by an increase in cardiac output
[26,27]. The resultant unloading of the carotid and
cardiopulmonary mechanoreceptors decreases the inhibitory input to the vasomotor centres with a consequent decrease in vagal tone and increase in sympathetic
outflow, resulting in an increase in cardiac chronotropic
and inotropic states and vasomotor tone. The initial HR
response to standing in young subjects is usually considered as bimodal with an immediate rise resulting from
abrupt inhibition of vagal activity followed by a more
gradual increase in HR resulting from an increase in
sympathetic outflow to the heart combined with vagal
inhibition. The HR response seems to be age-related, and
young subjects adjust to orthostatic stress mainly by a
marked increase in HR [27]. In accordance with observations in paced adults [28] and in children after
cardiac transplantation [4], our results demonstrated a
greater reduction in SBP in children with a fixed
ventricular rate. The lack of a cardiac component of the
rapid baroreflex response to standing up may explain this
transient hypotension. In our study, the magnitude of the
SBP drop observed in the control group was lower than
previously described in adults and in children over 10
years of age [29]. This discrepancy may be due to the
young age of our subjects given that only one was over 10
years old. Similarly, Yamagushi et al. [30] demonstrated a
less important BP fall in prepubescent children compared
with that of older counterparts during active standing.
Few data are available on the influence of age on dilator
responsiveness of vascular smooth muscle ; in this context, it should be noted that a low sympathetic basal
tone was evident in young animals [31] and children
[32].
The rapid BP increase after the initial reduction is due
to an increase in total peripheral resistance. The incremental rise in BP and the steady-state level of SBP
were similar in the two groups. These results demonstrate
that the regulation of peripheral vascular resistance can
compensate very quickly after the acute initial stress,
even in the absence of a HR response.
In conclusion, our study demonstrated that in stationary children with no functional autonomic control of
their sinus node, SBP variability was no different to that
observed in healthy control subjects. On the other hand,
our data revealed that the suppression of HR fluctuations
markedly reduced DBP fluctuations, especially in the
respiratory frequency range. This result suggests that, in
children, the vagally mediated HR fluctuations tend to
increase BP variability. However, during acute orthostatic stress, the rapid HR response induced by the
baroreflex system may contribute to the attenuation of
the BP reduction in healthy children.
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Received 30 October 1997/23 February 1998; accepted 23 February 1998
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