(Hypertension. 1995;25:1058-1068.)
© 1995 American Heart Association, Inc.
Articles |
Spontaneous Cardiac Baroreflex in Humans
Comparison With Drug-Induced Responses
From the Laboratoire de Physiologie de l'Environnement (CNRA SDI 6100 and URA 1341) and Département d'Anesthésie, Faculté de Médecine Grange Blanche and Hôpital Edouard Herriot, Lyon, France; and the Department of Kinesiology, University of Waterloo (Ontario, Canada).
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Abstract |
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Abstract We compared two methods of assessment of baroreflex sensitivity in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangents taken at the resting pressure of each of these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r=.96, P<.001), with significant but similar intraindividual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r=.69 to .83). The spontaneous baroreflex method provides a reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.
Key Words: pressoreceptors • blood pressure • heart rate • autonomic nervous system • clonidine • atropine • propranolol
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Introduction |
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Baroreceptor reflex control of heart rate is commonly quantified by vasoactive drug administration that raises or lowers systemic arterial pressure1 2 or by direct stimulation of carotid baroreceptors with neck chamber devices.3 These techniques have proved useful in a wide variety of experimental applications but are not appropriate in all clinical situations.4 5 A recently developed noninvasive technique of assessment of baroreflex sensitivity has been described in animals and humans.6 7 In this method, recordings of blood pressure (BP) and electrocardiograms are analyzed for the occurrence of sequences of spontaneously increasing or decreasing arterial pressures and the beat-by-beat effect on following cardiac intervals. This technique, referred to here as the spontaneous baroreflex (SBR) method, has been used in short-term and trend analyses of baroreflex slope and during exercise testing.8 9 Recently, baroreflex sensitivity calculated by the SBR method has been shown to correlate with values derived from power spectral analysis of heart rate and BP.10 Although a related method has been shown to correlate with the phenylephrine bolus technique in dogs,11 the SBR method has never been directly compared with the drug-induced method of cardiac baroreflex assessment in humans, in which heart rate responses induced by vasoactive drugs are evaluated. Since many factors are involved in the regulation of the cardiac baroreflex, such a comparison could help elucidate the similarities and contrasts between the physiological effects of spontaneous versus vasoactive drug–induced baroreflex responses. This would contribute to the rational choice of either method in any given experimental or clinical situation.
The objective of this study was to compare the cardiac baroreflex slope obtained by the method of SBR slope assessment with vasoactive drug–induced responses (drug-induced baroreflex) in healthy human volunteers. These comparisons were made during repeated baseline measures and during cardiac autonomic blockade using high doses of atropine, propranolol, and clonidine to induce a wide range of levels of autonomic activity.
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Methods |
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Subjects
This study was approved by the ethics review committee of the Hospices Civils de Lyon, and all procedures followed were in accordance with institutional guidelines. Having signed informed consent, eight healthy male physicians aged 25 to 46 years who were thoroughly familiar with our study environment participated in the study. None of the subjects had any abnormal findings on history, physical examination, or electrocardi- ography or were receiving any medications. All had normal resting brachial arterial BP measured by sphygmomanometer, with no significant difference between the two arms or significant orthostatic drop. All were instructed to avoid cigarettes, alcohol, and caffeine-containing beverages for 12 hours and strenuous exercise for 24 hours preceding each study.
Data Collection
During each manipulation, the electrocardiographic lead with the
greatest amplitude R wave and greatest signal-to-noise ratio (usually
lead V5) was continuously monitored by means of an
oscillographic monitor (VSM 1, Physio Control). Finger arterial BP was
measured by the volume-clamp method by means of a noninvasive
continuous BP monitor (Finapres 2300, Ohmeda). In this technique, a
plethysmographic cuff is placed around the middle phalanx of a finger,
and the cuff pressure is modulated to maintain transmural pressure at
effectively zero. In this way, variations in cuff pressure
represent the finger arterial pressure pulsations, and
quantitative continuous pressure waveforms are
generated.12 This monitor has been shown to provide a
reliable beat-by-beat measurement of systolic BP during a wide variety
of autonomic testing conditions when compared with intra-arterial
monitoring.12 13 The servo-reset mode of the Finapres was
turned off during the recordings and was reset between recordings.
Electrocardiogram and finger BP traces were continuously stored on
magnetic tape (Store 4, Racal) during all studies, with simultaneous
backups on a paper recorder (Dash 8, Astromed) during the vasoactive
drug injections.
Study Protocol
Manipulations were performed on three separate mornings
beginning at 8 AM on each of the eight subjects at
approximately 2-week intervals. All measurements were made with
subjects in the supine position in a quiet, darkened recovery room used
only for the present study. Subjects were instructed not to speak
during the recordings. An intravenous catheter was inserted into a
large forearm vein 1.5 hours before data collection. Measurements were
made according to the following schedule: Day 1: (1) at baseline (BL1),
(2) after parasympathetic blockade with 40 µg · kg-1
IV atropine sulfate, and (3) after ß-sympathetic blockade with 200
µg · kg-1 IV propranolol and a reinforcing dose of
10 µg · kg-1 IV atropine, ie, combined cardiac
autonomic blockade.14 Day 2: (1) at baseline (BL2), and
(2) after ß-sympathetic blockade with 200
µg · kg-1 IV propranolol. Day 3: (1) at baseline
(BL3), and (2) 120 minutes after oral ingestion of 6
µg · kg-1 clonidine hydrochloride.
During each study condition, a resting recording of at least 20 minutes in duration was performed for the calculation of mean SBR slope. For the drug-induced baroreflex, vasoactive drug injections were performed over the next 45 to 60 minutes. Serial intravenous bolus injections of the vasopressor phenylephrine hydrochloride and the vasodilator sodium nitroprusside were administered alternatively in increasing doses (30 to 1000 µg as necessary to raise or lower systolic pressure by 30 to 50 mm Hg). The maximal dose of each drug was repeated. Each injection was made over approximately 5 seconds and flushed through with 20 mL normal saline. Subjects were not informed as to the type or timing of drug injections. At least 5 minutes were allowed between injections for systolic pressure and RR interval to return fully to baseline values.
In this way, data were collected for each subject at three baseline periods, during isolated parasympathetic or ß-adrenoceptor sympathetic blockade, under combined cardiac blockade, and during central sympathetic inhibition with clonidine. The atropine and propranolol doses have been shown to provide a prolonged, complete autonomic-blocking effect.14 15 The clonidine dose used has been shown to provide significant reduction in sympathetic activity by hormonal and circulatory criteria.16 To ensure that the sympatholytic effects of propranolol were consistent over the duration of each period of data collection (about 90 minutes), we constructed isoproterenol dose-response curves17 for four subjects on a separate day at 15 and 90 minutes after the administration of 200 µg · kg-1 propranolol. Results showed no significant change in the heart rate response to isoproterenol (Student's t test, P>.05), indicating a comparable level of ß-sympathetic blockade throughout the procedure performed on day 2.
Data Analysis
All recordings were transferred off-line to a personal computer
(Compaq 386 SX) through a window-discriminator circuit set to detect R
wave peaks, with digitization by an analog-digital convertor (DAS-16G,
Metrabyte) at a sampling rate of 1000 Hz after appropriate calibration.
The recordings were observed on an oscilloscope during transfer for
later removal of any nonsinus beats or artifactual segments caused by
subject movement. The distances between all R wave peaks of the
electrocardiogram recording were thereby calculated to 1 millisecond of
accuracy, and these RR intervals (pulse intervals) were paired with the
systolic pressure wave amplitude of the preceding beat (ie, a one-beat
delay; Fig 1A).
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Spontaneous Method
For analysis of the 20-minute resting hemodynamic
recordings, the computer software selected all sequences of three or
more successive heart beats in which there were concordant increases or
decreases in systolic BP and RR interval (Fig 1A). A linear regression
was applied to each of the sequences, and an average regression slope
was calculated for the sequences detected during each recording period
(Fig 1B). This slope represents the cardiac baroreflex
sensitivity (in milliseconds per millimeter of mercury) by the SBR
method (SBR slope) for any study condition. Any instances of sequences
of increasing or decreasing systolic pressures with directionally
opposite changes in RR interval were recorded but not analyzed as they
do not represent physiological baroreflex responses.
Drug-Induced Baroreflex Method
After each vasoactive drug injection, coordinates of systolic
pressure and RR interval during the first phase of the pressure
response to the injection were considered. The data were handled in two
ways. First, the initial linear portions of the responses to
phenylephrine and nitroprusside were plotted separately. Values were
included from the initial pressure response to the maximal change in RR
interval. To eliminate the effect of normal spontaneous variation in
pressure and RR interval, we transformed these data using the methods
of Korner et al18 and Head and McCarty19 to
force all data to pass through the mean resting coordinates, defined as
the average of all preinjection values for that study period. Linear
regressions were applied to the initial linear portion of each series
of values1 20 ; those series with a correlation coefficient
of greater than .80 were considered. Data obtained from the injections
of the maximal dose for each of phenylephrine and nitroprusside that
fit these acceptance criteria were plotted. These linear regression
slopes were taken to represent the phenylephrine and
nitroprusside baroreflex slopes (Fig 2A).
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) and phenylephrine (
).
Coordinates are plotted from the average preinjection pressure during
the study period (broken arrow) to the maximal pressure change achieved
during the first phase of the response to each injection. A, Linear
regression lines are calculated for the linear portions of the data
obtained from the phenylephrine and nitroprusside injections
separately.Second, to obtain the sigmoidal baroreflex curves, we plotted together all points obtained during the first phase of the BP responses to bolus injections of phenylephrine and nitroprusside, including RR interval "plateau" points. After data transformation identical to that described above, systolic pressure values were then fitted to a sigmoidal logistic equation with the use of the Marquardt algorithm.18 21 A tangent to this sigmoid was derived numerically at the point of the mean preinjection systolic pressure of the series of phenylephrine and nitroprusside injections; this tangent represents the drug-induced baroreflex sensitivity calculated at the mean resting pressure (Fig 2B). Thus, for each study condition, three drug-induced parameters were obtained: a phenylephrine regression slope, a nitroprusside regression slope, and the slope of the tangent at the mean preinjection systolic pressure (drug-induced tangent).
Statistical Analysis
All data are expressed as mean±SEM unless otherwise stated. The
changes in mean values of resting RR interval and systolic pressure
were analyzed using a two-way ANOVA for repeated measurements. The
means of baroreflex sensitivity were analyzed using a MANOVA with a
two-factor design (subjects and study conditions, and subjects and
study methods). These analyses were performed on the log-transformed
data to take into account the skewed distribution of the data. In all
cases in which ANOVA showed significance, comparisons of means were
performed by Scheffé's test. A level of P<.05 was
chosen as significant. Regression between the SBR and the three
drug-induced slope values were examined using the least-squares method.
In addition, the SBR slopes were compared with drug-induced slopes
individually by plotting the differences between two methods against
the means of the methods.21 This method of
presentation allowed the calculation and demonstration of
between-method bias and the dispersion of differences in measured
parameters about the mean difference. Intraindividual variation for
each method was assessed by coefficients of variation for the three
baseline measurements.
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Results |
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Systolic Pressure and RR Interval
Mean resting levels of systolic pressure and RR interval did not differ significantly between the three different baseline studies. For all study conditions, mean resting values of systolic pressure and RR interval did not differ between the 20-minute period of SBR measurement and the average of the preinjection values during the period of drug-induced baroreflex measurements (Table 1). Atropine and combined cardiac autonomic blockade with atropine plus propranolol induced a significant decrease in resting RR interval, whereas propranolol alone and clonidine significantly increased resting RR interval. Atropine and combined blockade increased systolic pressure over baseline, whereas clonidine but not propranolol alone significantly decreased systolic pressure. Table 2 shows the ranges of spontaneous fluctuation of systolic pressure and RR interval during the 20-minute recording periods over which SBR sequences occurred.
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SBR Sequences
SBR sequences accounted for 20.9±2.9% of all cardiac cycles
occurring during each study period. In addition, a number of sequences
were identified in which BP and RR interval moved in opposite
directions; these sequences accounted for 9.6±1.0% of cardiac
cycles.
Baseline Variability
Analysis of intraindividual variability with respect to baseline
measurements on the three different study days revealed wide but
similar variability for all methods. Mean coefficients of variation for
each method were 25.0±3.7% (SBR slopes), 23.3±4.3% (drug-induced
tangents), 22.7±4.6% (phenylephrine slopes), and 23.8±4.2%
(nitroprusside slopes).
Comparison of Methods During Baseline and Autonomic Blockade
Fig 3 illustrates the data obtained in a complete
set of experiments on one typical subject (three baseline assessments
and four conditions of autonomic modification). The mean slope values
of eight subjects for each of the four methods during all seven study
conditions are listed in Table 3. Results obtained by
the SBR method did not differ statistically from the drug-induced
tangent method under any of the study conditions. The
phenylephrine slopes were significantly higher than the SBR and
drug-induced tangent values during atropine, combined blockade,
propranolol alone, and clonidine and for one of the three baseline
periods. The nitroprusside slopes were significantly lower than the SBR
and drug-induced tangent values except during blockade with atropine
alone or atropine plus propranolol.
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Average correlation coefficients of the SBR sequences within each study condition were always .92, as shown in Table 4. The regression curves obtained by the linear phenylephrine or nitroprusside curves or by the wide-range sigmoidal curves were also highly correlated to their respective linear or nonlinear models (Table 4).
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The variability in slopes within individual subjects from one study day to the next is shown in Fig 4 (left side of each panel). The changes in baroreflex slope in response to atropine (squares) and propranolol (circles) were similar for the spontaneous and drug-induced methods (right side of each panel), although two subjects (E and F) showed diverging responses to propranolol.
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) in eight subjects (A
through H). Broken lines illustrate effects obtained by the spontaneous
baroreflex (SBR) method; solid lines represent the drug-induced
baroreflex (tangent) method. Note the variability within each subject
of baseline SBR slope and drug-induced tangent between different days
of recording (left side of panels, eg, C and E). Note also the
similarity of response to both atropine and propranolol as measured by
either method, although two subjects (E and F) showed apparently
divergent responses to propranolol (see "Discussion").All methods revealed a major reduction in slopes during parasympathetic blockade with atropine and during combined blockade with atropine and propranolol. Although baroreflex slopes tended to increase with propranolol or clonidine alone when measured by all methods, the phenylephrine method led to significantly greater changes in slope. The change in baroreflex slope caused by propranolol correlated strongly with its effect on the resting RR interval for the SBR (r=.78, P<.05) and drug-induced tangent (r=.69, P=.06) methods only. Clonidine produced a similar correlation between change in baroreflex sensitivity and change in resting RR interval for the SBR (r=.77, P<.05) and drug-induced tangent (r=.83, P<.05) methods. There were no such significant correlations between the resting RR interval and either phenylephrine or nitroprusside slopes.
Regression analysis showed the SBR and drug-induced tangent methods to be highly correlated for the baseline periods, with a slope not significantly different from 1: SBR slope=-0.39+1.05xdrug-induced tangent (n=21, r=.96, P<.001, Fig 5). Conversely, for the same baseline periods, regression of SBR versus phenylephrine and SBR versus nitroprusside methods exhibited slopes that were significantly different from 1: SBR slope=1.46+0.79xphenylephrine slope (n=21, r=.72, P<.01); SBR slope=16.04+0.79xnitroprusside slope (n=21, r=.42, P<.05). For these two slopes, when all conditions were compared, the slope was still significantly different from 1. These discrepancies are further evidenced by Fig 6,22 which illustrates the between-method bias for SBR slopes against drug-induced tangent, phenylephrine, and nitroprusside slopes. Comparison of the SBR and drug-induced tangent methods (Fig 6A) shows negligible bias and very narrow dispersion about the mean difference. By contrast, the SBR slopes yielded a negative bias with respect to the phenylephrine slopes (Fig 6B) and a positive bias with respect to the nitroprusside slopes (Fig 6C); in these two comparisons, there is much wider dispersion about the mean difference.
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Discussion |
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In the present study, we assessed baroreflex slope from the analysis of sequences of spontaneous fluctuations of BP and RR interval selected using stringent criteria within resting values. This method provided very similar results to those obtained by deriving the slope at the average resting point of drug-induced baroreflex response curves. This similarity was consistent over time during repeated baseline measures and during induced extremes of autonomic blockade. This study is unique in three respects. First, the relatively new SBR method has been compared with drug-induced baroreflex responses in humans. Second, the use of selective autonomic blockade has helped to illustrate the relative influences of the parasympathetic and sympathetic systems on the baroreflex response as determined by the SBR method. Third, baroreflex slopes were taken at the mean preinjection systolic pressure of drug-induced sigmoidal curves in order to be compared with the SBR slopes and to yield information about baroreflex function under resting conditions.
SBR Method
The SBR sequence method was first used in unanesthetized
cats.6 The decrease in mean slope and frequency of
sequences after sinoaortic denervation attested to the
baroreflex-mediated nature of the RR interval response to spontaneous
fluctuations in BP. This response is presumed to be primarily under
parasympathetic control because of its extremely short latency,
evidenced by its beat-by-beat activity.23 Subsequent
studies in human subjects confirmed the occurrence of such sequences
and reported mean slopes that are reproducible9 but vary
significantly among subjects depending on subject
position9 and time of day.7 In our study,
many SBR sequences were detected during each 20-minute study period,
each sequence being composed of between three and seven points. The
sequences were highly linear, with mean correlation coefficients of .92
for each subject at each study condition (Table 4). This evidence,
along with their suppression after afferent denervation or cardiac
autonomic blockade, supports a true baroreflex nature of these
sequences rather than random coupling.6 10
SBR sequences accounted for approximately 20% of all cardiac cycles occurring during each study period. This figure is in keeping with previous studies in animals and humans.6 10 This suggests that approximately 80% of cardiac cycles are not involved in baroreflex responses, perhaps because in a controlled environment the baroreflex response is not frequently engaged or because these responses may occur rapidly within "sequences" of less than three beats. In addition, a number of sequences were identified in which BP and RR interval moved in opposite directions. These sequences accounted for about 10% of cardiac cycles and have been recognized in similar numbers in previous studies, although their significance has not been clearly established.6 10 The mean slope values of both SBR and drug-induced tangent methods obtained in the current study were higher than those of some previous studies. Factors accounting for this may include the supine positioning and low level of anxiety and stimulation of subjects during our protocol, as opposed to previous studies in which subjects were sitting9 24 or active.7 In one study in which subjects were tested in the supine position, the lower mean slope values may have been related to the 3-minute duration of recordings or to the different acceptance criteria for the segments, such as minimum four-beat sequences of ascending BP, and the presence of muscle sympathetic nerve activity bursts preceding the pressure increases.25
The use in the current study of a one-beat lag between beats of systolic pressures and their corresponding RR intervals (Fig 1A) has been supported by previous work using both the SBR9 25 and phenylephrine1 methods. The one-beat delay, compared with a delay of 0, +2, and +3 beats, has yielded a higher average correlation coefficient25 and a higher frequency of sequences,9 although this latter difference was not present with subjects in the standing position.
Drug-Induced Baroreflex Method
To obtain a valid comparison of the SBR method with the
drug-induced method, we took two factors into account in the
drug-induced baroreflex analysis. First, we considered the relative
influence of the sympathetic and parasympathetic systems. The initial
pulse interval response to bolus administration of both vasopressor and
vasodilator drugs has been shown to be primarily under parasympathetic
influence, with a much more delayed latency of onset of sympathetic
response.3 23 26 Clearly, the initial heart rate response
to vasopressors is parasympathetically mediated.23 27 28
The relative contribution of the parasympathetic and sympathetic
responses to vasodilators varies according to the timing of the
analysis. Studies measuring steady-state baroreflex sensitivity
with the use of vasodilators have demonstrated a blunting effect of
ß-receptor sympathetic blockade on the tachycardic
response.23 29 However, careful analysis of the time
lag in pulse interval response after nitroprusside injection has
revealed the initial pressure descent phase to be primarily due to
parasympathetic withdrawal, with sympathetic influences coming into
effect during the pressure recovery phase.26 In addition,
two phases have been identified in the response to neck suction and
pressure stimuli: in the early phase, propranolol had little effect on
blunting the tachycardic response, whereas during the late phase,
marked blunting occurred.3 In the present study,
parasympathetic blockade with atropine consistently decreased the slope
values at the average resting pressures on the drug-induced curves as
well as both the phenylephrine and nitroprusside slopes (Table 3).
Subsequent sympathetic blockade with propranolol did not reduce the
slopes further. Similarly, propranolol alone did not decrease any slope
measures. Therefore, the baroreflex slopes derived by the bolus drug
injection technique in the current study primarily reflected the
parasympathetic axis of the baroreflex response, enabling a rational
comparison of drug-induced versus SBR-derived values.
The second factor considered in the drug-induced baroreflex analysis was the nonlinear nature of the baroreflex response. The elucidation of the sigmoidal shape of the BP–RR interval relationship has made it apparent that in order to obtain a more physiological estimate of baroreflex sensitivity, a wide range in systolic pressure and RR interval must be evaluated and the locations of the plateaus and mean resting point determined.3 18 Indeed, a noncentral position of the resting pressure toward the lower plateau of the baroreflex response curve has been demonstrated in healthy young adults.3 Accordingly, in the present study, data were obtained during wide alterations in pressure, and points fitted closely to the sigmoidal regression model (Table 4).19 The average preinjection values of systolic pressure and RR interval for each series were used to unequivocally define a resting point on the sigmoidal curve, from which a tangent could be derived, since a large family of slopes could potentially be drawn from the same set of data. Therefore, a tangent taken at the point of the mean preinjection systolic pressure, regardless of where it fell in relation to the two plateaus of the curve, was taken to represent the average drug-induced baroreflex slope within the normal resting range of fluctuations of systolic pressure above and below this point. This slope could then more objectively be compared with the SBR slope, which represents the spontaneous function of the baroreceptor–heart rate reflex around the average resting pressure. The importance of this methodology was illustrated by some subjects in whom the phenylephrine portion of the drug-induced baroreflex curve was altered to a greater extent than the nitroprusside portion by sympathetic blockade (eg, Fig 3D). Here, the drug-induced baroreflex slope changed very little because of a shift of the mean resting coordinate toward a lower pressure and higher RR interval; the tangent at this point therefore remained on a relatively flatter portion of the sigmoid.
In the present study, data were plotted in terms of pulse interval (RR interval) instead of heart rate, following the precedent of all previously published reports using the SBR method6 7 8 9 10 11 24 25 and many studies using drug-induced techniques.1 2 3 18 30 However, the relationship between heart rate and RR interval is not linear, and thus baroreflex curves plotted using RR interval tend to compress data points in the portion of the curve of low RR interval (ie, during nitroprusside injections), leading to lower calculated slopes (eg, Fig 2). Similarly, separation between data points in the portion of the curve of high RR interval (ie, during phenylephrine injections) tends to be magnified (Fig 2), leading to higher calculated slopes. This may contribute to the bias toward lower nitroprusside slope values and higher phenylephrine slope values compared with data obtained by the SBR method (Fig 6B and 6C). The SBR slopes and drug-induced tangents are calculated using the same region of the baroreflex response curve at the level of resting systolic pressure and RR interval and thus would be less subject to bias introduced by the use of RR interval.
One methodological difference between the SBR and drug-induced methods relates to the intensity and rate at which the stimulus to baroreflex response is applied. In the spontaneous method, certain events lead to deviations in systolic pressure within a relatively narrow range, which lead to beat-by-beat changes in RR interval. Injections of vasoactive agents represent stimuli of much higher intensity in that they typically lead to far greater changes in systolic pressure and RR interval. In addition, each injection takes place over several seconds, and thus the rate of application of the stimulus may be different from that of the spontaneous method. Thus, either an intensity effect or a "rate sensitivity" effect of the system could potentially lead to different responses between the methods.
Baseline Variability
The intraindividual reproducibility of measurements of baroreflex
sensitivity over time has been shown to be quite variable when measured
by either the drug-induced or spontaneous
methods.1 5 7 30 Intraindividual differences of up to 27%
have been reported for baroreflex sensitivity measured several months
apart by the phenylephrine method.30 In addition,
large differences in average sensitivity have been demonstrated by the
SBR method over the course of the day.7 On the other hand,
a recent retrospective study has demonstrated good reproducibility
between pairs of measurements made 1 week or 10 weeks apart using the
neck chamber method.31 32 This might indicate that
variability is introduced at the level of other baroreceptor afferents,
such as aortic baroreceptors, or that the afferent responses are
modified by the neck chamber method itself.5 Whether the
variability shown in other studies represents a true
physiological phenomenon or the limits of error of the methods is
unclear. However, it is known that central influences, which presumably
vary within subjects over time, have a strong modifying effect on
central baroreflex control33 and on cardiac baroreflex
sensitivity.2 34 Thus, varying degrees of background
sympathetic activity might affect the beat-by-beat parasympathetic
control of heart rate. The present study found very similar
coefficients of variation of repeated baseline measures for the SBR and
drug-induced methods, with similar slope values for all measurement
periods. This argues for true biological variability in baroreflex
sensitivity, which is likely due to central or other external
influences present at the time of measurement, such as level of
mental relaxation or anxiety or external stimuli such as sudden noises
during the experimental period. Two points may be inferred from these
findings. First, long periods or frequently repeated assessments may
yield more information about an individual's baroreflex sensitivity
over a range of the subject's physiological conditions, as opposed to
measurement at a single point in time.7 Second, to obtain
valid comparisons of baroreflex sensitivity under different conditions,
eg, before and after a certain treatment, the measurements should be
made in a similar environment and closely in time. Variability in
repeated drug-induced measurements is much less when made approximately
30 minutes apart than those made at intervals of months.1
In the present study, we necessarily had to compare SBR and
drug-induced measurements obtained at different points in time;
however, these were separated by at most 60 minutes within each study
condition, so that a valid between-method comparison could be
inferred.
Effect of Cardiac Autonomic Blockade
As in previous studies,2 27 35 parasympathetic
blockade with atropine led to a flattening of cardiac baroreflex slopes
obtained by all four methods. The subsequent addition of propranolol
(ie, combined blockade) showed a trend back toward an increase in
sensitivity, especially when measured by the phenylephrine and
drug-induced tangent methods, although this change did not reach
significance. The fact that there remained any RR interval response
after parasympathetic and combined antagonism may have reflected some
residual autonomic activity, despite the use of atropine and
propranolol doses previously shown to be sufficient.14 15
Alternatively, reflex responses via other pathways or intracardiac
reflexes might be postulated. The trend toward an increase in slope
with combined block could conceivably be explained by a diminished
effect of atropine over the course of the study period, although a
reinforcing dose of atropine had been given immediately after
propranolol administration. Such a slope-enhancing effect of the
addition of propranolol has previously been observed2 and
may be a result of the withdrawal of sympathetic inhibitory influences
on the baroreflex mechanism34 or related to the increased
baseline RR interval after propranolol (Table 1).1 36
Propranolol alone had variable effects on baroreflex sensitivity depending on the method of measurement (Table 3), and there was considerable intersubject variability (Fig 4E and 4F). Several studies have examined the effects of propranolol on baroreflex function, showing enhancement of the slope during phenylephrine-induced hypertension2 or simulated hypertension using neck suction.3 34 On the other hand, hypotension induced by vasodilators or simulated by neck pressure has led to variable responses.3 35 In the present study, the degree of effect of propranolol on baroreflex slope strongly correlated with its degree of effect on RR interval, a finding noted in previous studies.34 37 The increase in baroreflex slope with propranolol may be explained by its peripheral, and possibly central, blockade of sympathetic influences that ordinarily blunt parasympathetic control of the sinus node and thereby diminish the range of the RR interval response to pressure changes.5 34 Alternatively, propranolol has been proposed to have a more direct parasympathetic-enhancing effect.38 This correlation between the change in baroreflex slope and the change in baseline RR interval was only noted during the SBR and drug-induced tangent methods; in these two methods, the baroreflex slope was by definition measured with reference to the average resting pressure. Resetting of the curve that might occur during propranolol treatment may make these measurements more sensitive to changes in slope at the changing resting level of pressure and thus suggests a much closer similarity in the physiological responses measured by the SBR and tangent methods compared with phenylephrine and nitroprusside boluses alone. The nitroprusside and phenylephrine linear slopes alone tend to measure the region of the lower plateau and the maximal slope of the sigmoid, respectively, and thus are not indexed to the resting systolic pressure. However, in two subjects, the SBR and drug-induced tangent slopes did not change in a parallel fashion with propranolol (Fig 4E and 4F, circles); a similar observation was made in one subject with clonidine. In these individuals, the relatively greater increase in the phenylephrine portion of the sigmoid led to a very steep lower curvature (as in Fig 3D). Since the average resting pressure frequently occurs on this portion of the sigmoid,3 very small differences in systolic pressure may thus lead to large changes in the slope of the tangent to this point. The SBR slope on the other hand represents an averaged baroreflex sensitivity within the range of spontaneous fluctuation around the resting pressure measured over 20 minutes in the resting state and is thus less sensitive to small changes in resting pressure. It must be noted again that baroreflex response curves using RR interval as opposed to heart rate tend to amplify changes in slope in the region of high RR interval and thus may magnify the effects of phenylephrine injection during sympathetic blockade, which prolongs baseline RR interval.
The 
2-adrenergic agonist clonidine was used for its
primary effect of reducing central sympathetic outflow without a
significant direct effect on peripheral - and ß-adrenergic
receptors. It may also have a central parasympathetic-enhancing
effect.39 Clonidine produced results very similar to those
of propranolol (Table 3), further supporting the hypothesis that
sympathetic influences, whether central or peripheral in nature, act in
an opposing direction to parasympathetic baroreflex control. As with
propranolol, there was marked intersubject variability in the degree of
change in slope, with the effect on baroreflex sensitivity correlating
strongly with the effect on resting RR interval for the SBR and
drug-induced tangent methods. Few studies have investigated the effects
of clonidine on the baroreflex in normotensive subjects. Clonidine did
not lead to a significant increase in the heart rate response to graded
nitroprusside infusion.40 In hypertensive individuals,
rapid intravenous injection of clonidine produced no increase in
baroreflex sensitivity as measured by neck suction or
pressure,39 but orally administered clonidine led to an
increase in slope averaging 78% in 26 of 30 patients as measured by
the phenylephrine bolus technique.41 A dose-dependent
increase in baroreflex gain has been demonstrated in normotensive and
renal hypertensive rabbits after clonidine; this effect was impaired
after vagotomy.42 Since the methods we have used in the
current study appear to measure primarily the parasympathetic response
to changes in BP, our finding of an augmentation of baroreflex
sensitivity with clonidine supports an enhancement of the vagal
baroreflex response, possibly by decreasing the prevailing level of
sympathetic tone.39 42
Advantages and Limitations of the Drug-Induced and SBR Methods
The usefulness and constraints of traditionally used methods of
baroreflex assessment have been reviewed elsewhere.4 5
Some investigators have even viewed the traditional drug-induced
baroreflex as misleading.43 Both techniques can be used
with either noninvasive or intra-arterial continuous BP monitoring. The
Finapres apparatus has been shown to accurately reflect intra-arterial
pressure during a range of tests of autonomic
function.12 13 Neither traditional drug-induced baroreflex
assessment nor the SBR method take into account the other input
variables besides systolic and mean pressure that are involved in
baroreflex regulation of RR interval, such as diastolic pressure, pulse
pressure, stroke volume, and dP/dt. Other nonarterial baroreceptor
afferents that respond to changes in arterial pressure are ignored, as
is the vasomotor efferent arm of the baroreflex system. It is difficult
to control for all of these variables with either of the described
methods. The cardiac baroreflex can be assumed to provide a buffer
solely against short-term disturbances in BP only under resting
conditions with low levels of stimulation. By contrast, it can be
overridden or reset to higher pressures during rapid rises in heart
rate in response to a variety of stimuli, such as exercise or the
defense reaction. Thus, the SBR and drug-induced tangent methods, as
used in the present study, have been shown to be closely correlated
only under resting conditions with low levels of external and internal
stimulation in supine healthy volunteers. Finally, some technical
problems preclude the use of the SBR technique, although these may
apply equally to the other methods. These may be caused by cardiac
arrhythmias, such as frequent extrasystoles or atrial fibrillation, and
movement artifacts in uncooperative subjects.
The SBR method has a number of important advantages. First, it does not require the use of drugs or a neck chamber apparatus. Second, it measures baroreflex sensitivity in the normal physiological range over a period of time rather than brief and extreme perturbations as induced by other methods. In this respect, it represents a true steady-state assessment of the cardiac baroreflex under stationary conditions, during which the sequences are selected within a range of resting values. The method differs from the steady-state method described previously,18 20 which examines the maximal changes in RR interval observed at peak pressure changes 15 to 30 seconds after the onset of the pressure change, and takes into account the full extent of combined parasympathetic and sympathetic influences under dynamic conditions. Third, the SBR method is noninvasive when used with noninvasive continuous BP monitoring and requires little subject cooperation or stress. Thus, it can be used frequently for serial measurements and over time for trend analysis in mobile subjects.7
Several important limitations of the technique also exist. It requires fairly long periods of recording (>10 minutes), although this may lead to a more accurate averaged baroreflex slope than that obtained by a single induced baroreceptor stimulus. Information about baroreflex function is limited to the physiological gain and resting points, and the overall reflex parameters, such as the range of RR interval response, level of the upper and lower plateaus, and gain at midrange, are not evaluated.18 29 This is due to two inherent limitations of the SBR method: the inability to achieve "full-range analysis," and the consideration of only the rapid parasympathetic component of the response during a sequence, which is usually too short to fully grasp the slower sympathetic component. Thus, the SBR method does not reflect changes in certain properties of the baroreflex, such as distinguishing shifts of the set point along the curve from resetting of the whole curve to a different level.42 Indeed, the fact that the range cannot be evaluated precludes the overall quantitative estimation of the size of recruitable cardiac parasympathetic motorneurons and sympathetic premotorneurons. The SBR method, derived from the use of time series analysis, considers the central organization of the cardiac parasympathetic and sympathetic reflex as a "black box." This black box approach is even more true in the present article, which deals only with validation of a method and not with theoretical questions concerning the organization of the central circulatory network. Furthermore, the difference between the SBR slope and the drug-induced slopes may reflect different aspects of the cardiac baroreflex. The gain of the drug-induced baroreflex is an index of the maximal recruitment of cardiac vagal motorneurons during extremes of parasympathetic engagement with very large excursions of pressure. This slope thus quantifies the phasic reflex cardiac baroreflex activity, presumably predominantly parasympathetically mediated. By contrast, the gain of the SBR slope indicates the minimal recruitment by natural pressure stimuli of only cardiac vagal motorneurons under baseline resting conditions. Thus, the SBR slope quantifies the tonic cardiac parasympathetic baroreflex activity.
We conclude that SBR assessment provides values of cardiac baroreflex sensitivity similar to those obtained with the drug-induced method, within the physiological range of BP under resting conditions. SBR control of heart rate appears to be chiefly under parasympathetic regulation and is inhibited by sympathetic influences. The SBR method is noninvasive when used with noninvasive continuous BP monitoring and is reliable within a wide range of levels of autonomic activity. It may prove to be a useful method of assessment of vagal cardiac baroreflex sensitivity in patients in whom other methods may be unsuitable.
|
Acknowledgments |
|---|
Supported by INSERM (CNEP 89.48, 91.43, 94.11), Université Claude Bernard de Lyon, CNRS (PRA), the Janssen fellowship of the Canadian Anaesthetists' Society, the Royal College of Physicians and Surgeons of Canada, and a Région Rhône-Alpes/MRC Canada Visiting Scientist Award. We thank Pr Paul Petit, Drs Pierre Sagnard and Michael Adams, and Jean Frutoso for their assistance.
|
Footnotes |
|---|
Reprint requests to L. Quintin, Physiologie, Faculté de Médecine, 69373 Lyon 08, France.
Received December 27, 1993; first decision January 27, 1994; accepted December 16, 1994.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Smyth HS, Sleight P, Pickering GW. Reflex regulation of arterial pressure during sleep in man. Circ Res. 1969;24:109-121.
2.
Pickering TG, Gribbin B, Strange Petersen E,
Cunningham DJC, Sleight P. Effects of autonomic blockade on
the baroreflex in man at rest and during exercise.
Circ Res. 1972;30:177-185.
3.
Eckberg DL. Nonlinearities of the human carotid
baroreceptor-cardiac reflex. Circ Res. 1980;47:208-216.
4. Eckberg DL. Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol. 1980;239:H581-H593.
5. Mancia G, Mark AL. Arterial baroreflexes in humans. In: Shepherd JT, Abboud Im, eds. Handbook of Physiology, Section 2: The Cardiovascular System, Vol III, Peripheral Circulation and Organ Blood Flow. Bethesda, Md: American Physiological Society; 1983;755-794.
6.
Bertinieri G, Di Rienzo M, Cavallazzi A, Ferrari AU,
Pedotti A, Mancia G. Evaluation of baroreceptor reflex by blood
pressure monitoring in unanesthetized cats. Am J
Physiol. 1988;254:H377-H383.
7. Parati G, Di Rienzo M, Bertinieri G, Pomidossi G, Casadei R, Groppelli A, Pedotti A, Zanchetti A, Mancia G. Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans. Hypertension. 1988:12:214-219.
8.
McDonald MP, Sanfilippo AJ, Savard GK.
Baroreflex function and cardiac structure with moderate
endurance training in normotensive men. J Appl
Physiol. 1993;74:2469-2477.
9. Steptoe A, Vogele C. Cardiac baroreflex function during postural change assessed using non-invasive spontaneous sequence analysis in young men. Cardiovasc Res. 1990;24:627-632.
10. Hughson RL, Quintin L, Annat G, Yamamoto Y, Gharib C. Spontaneous baroreflex by sequence and power spectral methods in humans. Clin Physiol. 1993;13:663-676. [Medline] [Order article via Infotrieve]
11.
Frankel RA, Metting PJ, Britton SL. Evaluation
of spontaneous baroreflex sensitivity in conscious dogs.
J Physiol (Lond). 1993;462:31-45.
12.
Imholz BPM, Settels JJ, van der Meiracker AH, Wesseling
KH, Wieling W. Non-invasive continuous finger blood pressure
measurement during orthostatic stress compared to intra-arterial
pressure. Cardiovasc Res. 1990;24:214-221.
13.
Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia
G. Comparison of finger and intra-arterial blood pressure
monitoring at rest and during laboratory testing.
Hypertension. 1989;13:647-655.
14. Jose AD, Taylor RR. Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. J Clin Invest. 1969;48:2019-2030.
15. Epstein RL, Robinson BF, Kahler RL, Braunwald E. Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J Clin Invest. 1965;44:1745-1753.
16.
Reid IA, Nolan PL, Wolf JA, Keil LC. Suppression
of vasopressin secretion by clonidine: effect of alpha-adrenoceptor
antagonists. Endocrinology. 1979;104:1403-1406.
17.
Cleaveland CR, Rangno RE, Shand DG. A
standardized isoproterenol sensitivity test. Arch Intern
Med. 1972;130:47-52.
18. Korner PI, West MJ, Shaw J, Uther JB. `Steady-state' properties of the baroreceptor-heart rate reflex in essential hypertension in man. Clin Exp Pharmacol Physiol. 1974;1:65-76. [Medline] [Order article via Infotrieve]
19. Head GA, McCarty R. Vagal and sympathetic components of the heart rate range and gain of the baroreceptor-heart rate reflex in conscious rats. J Auton Nerv Syst. 1987;21:203-213. [Medline] [Order article via Infotrieve]
20. Pickering TG, Gribbin B, Sleight P. Comparison of the reflex heart rate response to rising and falling arterial pressure in man. Cardiovasc Res. 1972;6:277-283.[Medline] [Order article via Infotrieve]
21.
Kingwell BA, McPherson GA, Korner PI. Assessment
of gain of tachycardia and bradycardia responses of cardiac
baroreflex. Am J Physiol. 1991;260:H1254-H1263.
22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307-310. [Medline] [Order article via Infotrieve]
23.
Coleman TG. Arterial baroreflex control of heart
rate in the conscious rat. Am J Physiol. 1980;238:H515-H520.
24. Steptoe A, Sawada Y. Assessment of baroreceptor reflex function during mental stress and relaxation. Psychophysiology. 1989;26:140-147. [Medline] [Order article via Infotrieve]
25.
Fritsch JM, Eckberg DL, Graves LD, Wallin BG.
Arterial pressure ramps provoke linear increases of heart period
in humans. Am J Physiol. 1986;251:R1086-R1090.
26. Chen RYZ, Fan F, Schuessler GB, Chien S. Baroreflex control of heart rate in humans during nitroprusside-induced hypotension. Am J Physiol. 1982;243:R18-R24.
27.
Casadei R, Meyer TE, Coats AJS, Conway J, Sleight P.
Baroreflex control of stroke volume in man: an effect mediated
by the vagus. J Physiol (Lond). 1992;448:539-550.
28. Greene NM, Bachand RG. Vagal component of the chronotropic response to baroreceptor stimulation in man. Am Heart J. 1971;82:22-27. [Medline] [Order article via Infotrieve]
29. Kingwell BA, Dart AM, Jennings GL, Korner PI. Exercise training reduces the sympathetic component of the blood pressure-heart rate baroreflex in man. Clin Sci. 1992;82:357-362. [Medline] [Order article via Infotrieve]
30.
Gribbin B, Pickering TG, Sleight P, Peto R.
Effect of age and high blood pressure on baroreflex sensitivity
in man. Circ Res. 1971;29:424-431.
31.
Eckberg DL, Convertino VA, Fritsch JM, Doerr DF.
Reproducibility of human vagal carotid
baroreceptor-cardiac reflex responses. Am J
Physiol. 1992;263:R215-R220.
32.
Sanders JS, Mark AL, Ferguson DW.
Importance of baroreflex in regulation of sympathetic responses
during hypotension. Circulation. 1989;79:83-92.
33. Tadepalli AS, Mills E, Schanberg SM. Depression and enhancement of baroreceptor pressor response in cats after intracerebroventricular injection of noradrenergic blocking agents. Circ Res. 1976;39:726-730.
34.
Eckberg DL, Abboud FM, Mark AL. Modulation of
carotid baroreflex responsiveness in man: effects of posture and
propranolol. J Appl Physiol. 1976;41:383-387.
35. Glick G, Braunwald E. Relative roles of the sympathetic and parasympathetic nervous systems in the reflex control of heart rate. Circ Res. 1964;16:363-375.
36. Watson RDS, Stallard TS, Littler WA. Effects of beta-adrenoceptor antagonists on sinoaortic baroreflex sensitivity and blood pressure in hypertensive man. Clin Sci. 1979;57:241-247. [Medline] [Order article via Infotrieve]
37. Bristow JD, Brown EB, Cunningham DJC, Howson MG, Strange-Petersen E, Pickering TG, Sleight P. Effect of bicycling on the baroreflex regulation of pulse interval. Circ Res. 1971;28:582-592.
38. Eckberg DL. Beta-adrenergic blockade may prolong life in post-infarction patients in part by increasing vagal cardiac inhibition. Med Hypotheses. 1984;15:421-432. [Medline] [Order article via Infotrieve]
39.
Mancia G, Ferrari A, Gregorini L, Zanchetti A.
Clonidine and carotid baroreflex in essential
hypertension. Hypertension. 1979;1:362-370.
40. McLean AJ, Gelman J, Hargreaves M, Jennings GL. Interaction of alpha-methyldopa with autonomic reflex tachycardia in man. J Cardiovasc Pharmacol. 1983;5:638-642. [Medline] [Order article via Infotrieve]
41. Guthrie GP, Kotchen TA. Effects of oral clonidine on baroreflex function in patients with essential hypertension. Chest. 1983;83(suppl):327-328.
42. Korner PI, Oliver JR, Sleight P, Robinson JS, Chalmers JP. Assessment of cardiac autonomic excitability in renal hypertensive rabbits using clonidine-induced resetting of the baroreceptor-heart rate reflex. Eur J Pharmacol. 1975;33:353-362. [Medline] [Order article via Infotrieve]
43. Ludbrook J. Concern about gain: is this the best measure of performance of cardiovascular reflexes? Clin Exp Pharmacol Physiol. 1984;11:385-390.[Medline] [Order article via Infotrieve]
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V. Gross, J. Tank, M. Obst, R. Plehm, K. J. Blumer, A. Diedrich, J. Jordan, and F. C. Luft Autonomic nervous system and blood pressure regulation in RGS2-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1134 - R1142. [Abstract] [Full Text] [PDF]
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B. E. Hunt and W. B. Farquhar Nonlinearities and asymmetries of the human cardiovagal baroreflex Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1339 - R1346. [Abstract] [Full Text] [PDF]
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G. J. Gates, S. E. Mateika, R. C. Basner, and J. H. Mateika Baroreflex Sensitivity in Nonapneic Snorers and Control Subjects Before and After Nasal Continuous Positive Airway Pressure Chest, September 1, 2004; 126(3): 801 - 807. [Abstract] [Full Text] [PDF]
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I. Constant, D. Laude, E. Hentzgen, and I. Murat Does Halothane Really Preserve Cardiac Baroreflex Better Than Sevoflurane? A Noninvasive Study of Spontaneous Baroreflex in Children Anesthetized with Sevoflurane Versus Halothane Anesth. Analg., August 1, 2004; 99(2): 360 - 369. [Abstract] [Full Text] [PDF]
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 M. Tanaka, T. Kimura, T. Goyagi, and T. Nishikawa Gender differences in baroreflex response and heart rate variability in anaesthetized humans Br. J. Anaesth., June 1, 2004; 92(6): 831 - 835. [Abstract] [Full Text] [PDF]
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G. Parati, M. Di Rienzo, P. Castiglioni, M. Bouhaddi, C. Cerutti, A. Cividjian, J.-L. Elghozi, J.-O. Fortrat, A. Girard, B. J.A. Janssen, et al. Assessing the Sensitivity of Spontaneous Baroreflex Control of the Heart: Deeper Insight Into Complex Physiology * Response Hypertension, May 1, 2004; 43(5): e32 - e34. [Full Text] [PDF]
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 F. Costes, F. Roche, V. Pichot, J.M. Vergnon, M. Garet, and J-C. Barthelemy Influence of exercise training on cardiac baroreflex sensitivity in patients with COPD Eur. Respir. J., March 1, 2004; 23(3): 396 - 401. [Abstract] [Full Text] [PDF]
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 D. Kaya, I. Barutcu, A. M. Esen, E. Onrat, A. Orman, and M. Unlu Comparison of the effects of ipratropium bromide and salbutamol on autonomic heart rate control Europace, January 1, 2004; 6(6): 602 - 607. [Abstract] [Full Text] [PDF]
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M. Tanaka, M. Sato, S. Umehara, and T. Nishikawa Influence of menstrual cycle on baroreflex control of heart rate: comparison with male volunteers Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1091 - R1097. [Abstract] [Full Text] [PDF]
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F. Yamazaki and K. Hamasaki Heat acclimation increases skin vasodilation and sweating but not cardiac baroreflex responses in heat-stressed humans J Appl Physiol, October 1, 2003; 95(4): 1567 - 1574. [Abstract] [Full Text] [PDF]
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T. Gori, J. S. Floras, and J. D. Parker Effects of nitroglycerin treatment on baroreflex sensitivity andshort-term heart rate variability in humans J. Am. Coll. Cardiol., December 4, 2002; 40(11): 2000 - 2005. [Abstract] [Full Text] [PDF]
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 A J M Broadley, A Korszun, C J H Jones, and M P Frenneaux Arterial endothelial function is impaired in treated depression Heart, December 1, 2002; 88(5): 521 - 523. [Abstract] [Full Text] [PDF]
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 M. R. Bonsignore, G. Parati, G. Insalaco, O. Marrone, P. Castiglioni, S. Romano, M. Di Rienzo, G. Mancia, and G. Bonsignore Continuous Positive Airway Pressure Treatment Improves Baroreflex Control of Heart Rate during Sleep in Severe Obstructive Sleep Apnea Syndrome Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 279 - 286. [Abstract] [Full Text] [PDF]
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V. Gross, R. Plehm, J. Tank, J. Jordan, A. Diedrich, M. Obst, and F. C. Luft Heart Rate Variability and Baroreflex Function in AT2 Receptor-Disrupted Mice Hypertension, August 1, 2002; 40(2): 207 - 213. [Abstract] [Full Text] [PDF]
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I. Constant, M. Abbas, S. Boucheseiche, D. Laude, and I. Murat Non-invasive assessment of cardiovascular autonomic activity induced by brief exposure to 50% nitrous oxide in children Br. J. Anaesth., May 1, 2002; 88(5): 637 - 643. [Abstract] [Full Text] [PDF]
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S. D. Beske, G. E. Alvarez, T. P. Ballard, and K. P. Davy Reduced cardiovagal baroreflex gain in visceral obesity: implications for the metabolic syndrome Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H630 - H635. [Abstract] [Full Text] [PDF]
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M Nakagawa, N Takahashi, T Ooie, K Yufu, M Hara, M Watanabe, S Nobe, H Yonemochi, I Katsuragi, T Okeda, et al. Development of a new method for assessing the cardiac baroreflex: response to downward tilting in patients with diabetes mellitus Heart, December 1, 2001; 86(6): 643 - 648. [Abstract] [Full Text] [PDF]
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 L. Mangin, A. Monti, C. Medigue, I. Macquin-Mavier, M.-E. Lopes, P. Gueret, A. Castaigne, B. Swynghedauw, and P. Mansier Altered baroreflex gain during voluntary breathing in chronic heart failure Eur J Heart Fail, March 1, 2001; 3(2): 189 - 195. [Abstract] [Full Text] [PDF]
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N. D. Avery, L. A. Wolfe, C. E. Amara, G. A. L. Davies, and M. J. McGrath Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold J Appl Physiol, January 1, 2001; 90(1): 321 - 328. [Abstract] [Full Text] [PDF]
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 F. Iellamo, J. M. Legramante, M. Massaro, G. Raimondi, and A. Galante Effects of a Residential Exercise Training on Baroreflex Sensitivity and Heart Rate Variability in Patients With Coronary Artery Disease : A Randomized, Controlled Study Circulation, November 21, 2000; 102(21): 2588 - 2592. [Abstract] [Full Text] [PDF]
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W. H. Cooke, J. E. Ames IV, A. A. Crossman, J. F. Cox, T. A. Kuusela, K. U. O. Tahvanainen, L. B. Moon, J. Drescher, F. J. Baisch, T. Mano, et al. Nine months in space: effects on human autonomic cardiovascular regulation J Appl Physiol, September 1, 2000; 89(3): 1039 - 1045. [Abstract] [Full Text] [PDF]
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P. Van de Borne, S. Mezzetti, N. Montano, K. Narkiewicz, J. P. Degaute, and V. K. Somers Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H536 - H541. [Abstract] [Full Text] [PDF]
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J. P. Fauvel, C. Cerutti, P. Quelin, M. Laville, M. P. Gustin, C. Z. Paultre, and M. Ducher Mental Stress-Induced Increase in Blood Pressure Is Not Related to Baroreflex Sensitivity in Middle-Aged Healthy Men Hypertension, April 1, 2000; 35(4): 887 - 891. [Abstract] [Full Text] [PDF]
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 D. Mesangeau, D. Laude, and J.-L. Elghozi Early detection of cardiovascular autonomic neuropathy in diabetic pigs using blood pressure and heart rate variability Cardiovasc Res, March 1, 2000; 45(4): 889 - 899. [Abstract] [Full Text] [PDF]
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 E. Toussirot, M. Bahjaoui-Bouhaddi, J.-C. Poncet, S. Cappelle, M.-T. Henriet, D. Wendling, and J. Regnard Abnormal autonomic cardiovascular control in ankylosing spondylitis Ann Rheum Dis, August 1, 1999; 58(8): 481 - 487. [Abstract] [Full Text]
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F. Iellamo, P. Pizzinelli, M. Massaro, G. Raimondi, G. Peruzzi, and J. M. Legramante Muscle Metaboreflex Contribution to Sinus Node Regulation During Static Exercise : Insights From Spectral Analysis of Heart Rate Variability Circulation, July 6, 1999; 100(1): 27 - 32. [Abstract] [Full Text] [PDF]
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N. Takahashi, M. Nakagawa, T. Saikawa, T. Ooie, T. Akimitsu, K. Kaneda, M. Hara, T. Iwao, H. Yonemochi, M. Ito, et al. Noninvasive assessment of the cardiac baroreflex: Response to downward tilting and comparison with the phenylephrine method J. Am. Coll. Cardiol., July 1, 1999; 34(1): 211 - 215. [Abstract] [Full Text] [PDF]
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G. Mancia, G. Parati, P. Castiglioni, and M. di Rienzo Effect of sinoaortic denervation on frequency-domain estimates of baroreflex sensitivity in conscious cats Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1987 - H1993. [Abstract] [Full Text] [PDF]
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L. Rudas, A. A. Crossman, C. A. Morillo, J. R. Halliwill, K. U. O. Tahvanainen, T. A. Kuusela, and D. L. Eckberg Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1691 - H1698. [Abstract] [Full Text] [PDF]
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D. Sigaudo, J.-O. Fortrat, A.-M. Allevard, A. Maillet, J.-M. Cottet-Emard, A. Vouillarmet, R. L. Hughson, G. Gauquelin-Koch, and C. Gharib Changes in the sympathetic nervous system induced by 42 days of head-down bed rest Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H1875 - H1884. [Abstract] [Full Text] [PDF]
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M. V. Pitzalis, F. Mastropasqua, A. Passantino, F. Massari, L. Ligurgo, C. Forleo, C. Balducci, F. Lombardi, and P. Rizzon Comparison Between Noninvasive Indices of Baroreceptor Sensitivity and the Phenylephrine Method in Post–Myocardial Infarction Patients Circulation, April 14, 1998; 97(14): 1362 - 1367. [Abstract] [Full Text] [PDF]
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P. B. Persson Spectrum analysis of cardiovascular time series Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1997; 273(4): R1201 - R1210. [Abstract] [Full Text] [PDF]
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S. Y. Kim and D. E. Euler Baroreflex Sensitivity Assessed by Complex Demodulation of Cardiovascular Variability Hypertension, May 1, 1997; 29(5): 1119 - 1125. [Abstract] [Full Text]
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 E. Drouin, V. Gournay, J. Calamel, A. Mouzard, and J.-C. Rozé Assessment of spontaneous baroreflex sensitivity in neonates Arch. Dis. Child. Fetal Neonatal Ed., March 1, 1997; 76(2): 108F - 112. [Abstract] [Full Text]
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L. L. Watkins, P. Grossman, and A. Sherwood Noninvasive Assessment of Baroreflex Control in Borderline Hypertension: Comparison With the Phenylephrine Method Hypertension, August 1, 1996; 28(2): 238 - 243. [Abstract] [Full Text]
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