From the Hebrew Rehabilitation Center for Aged Research and Training
Institute (L.A.L., R.J.M.), the Beth Israel/Deaconess Medical Center
Department of Medicine, Harvard Medical School, Boston, Mass (L.A.L.); and
Nagoya City University Medical School, Nagoya, Japan (J.H., S.S., A.O.).
Correspondence to Lewis A. Lipsitz, MD, Hebrew Rehabilitation Center for Aged, 1200 Centre St, Boston, MA 02131. E-mail Lipsitz{at}mail.hrca.harvard.edu
Methods and Results—We used complex demodulation to continuously
assess changes in respiration, R-R interval, and arterial
pressure (blood pressure) variability during 60 degree head-up tilt in
25 healthy subjects with tilt-induced vasovagal syncope and 25
age-matched nonsyncopal control subjects. Coherence and transfer
function analyses were used to examine the relation between
respiration and R-R interval variability before syncope. Baseline blood
pressure, R-R, and ventilation were similar between syncope subjects
and control subjects. Syncope subjects experienced an increase in tidal
volume and decrease in BP beginning 3 minutes before impending syncope
(systolic blood pressure <80 mm Hg) necessitated
termination of tilt. Approximately 90 seconds before syncope there was
a sudden prolongation of R-R interval and increase in amplitude of high
and low frequency R-R interval variability, indicating an abrupt
enhancement of vagal tone. The increase in respiratory amplitude
between 180 and 90 seconds before syncope was not accompanied by
changes in R-R interval or R-R variability, suggesting a dissociation
between respiration and the respiratory sinus arrhythmia. The
coherence analysis showed fewer syncope subjects with coherence
between respiratory and R-R interval variabilities and lower transfer
magnitudes in syncope subjects compared with control subjects.
Nonsyncopal subjects had no change in respiratory, R-R interval, or
blood pressure dynamics during matched time periods before the time of
syncope.
Conclusions—Vasovagal syncope is preceded by a period of
hyperpnea and cardiorespiratory decoupling followed by an abrupt
increase in cardiovagal tone. Respiratory pumping without inspiratory
cardiac slowing may partially counteract preload reduction until sudden
bradycardia precipitates syncope.
Frequency domain (Fourier) analysis of cardiac interbeat
interval (R-R) variability has been widely used to assess autonomic
control of cardiovascular
function.4 High-frequency variability in the
range of 0.15 to 0.45 Hz results almost exclusively from
respiration-related vagal modulation of heart rate, and its amplitude
has been used as an index of vagal tone.5 6 Low
frequency variability between 0.04 and 0.15 Hz probably reflects the
effects of both respiration and baroreflex-mediated sympathetic outflow
on the heart.4 Fourier analysis of R-R
interval variability is appealing for the assessment of autonomic
mechanisms underlying syncope; however, its interpretation is
confounded by alterations in respiratory frequency and amplitude that
may precede the development of symptoms. Furthermore, this technique
cannot be used to assess sudden, time-dependent changes in the
amplitude of a particular frequency. Recently, the technique of complex
demodulation has been developed to provide a continuous assessment of
the amplitude of cardiovascular variabilities and
thereby identify changing autonomic responses to
cardiovascular events.7 We used
this method to investigate alterations in cardiac interbeat interval
and respiratory dynamics preceding vasovagal syncope and their relation
to each other. Since vasovagal syncope is thought to be due to a sudden
increase in vagal outflow from the central nervous system, we
hypothesized that there would be a marked increase in high frequency
R-R interval variability preceding the development of tilt-induced
syncope and that this increase would be independent of respiration.
The study was approved by the Institutional Review Board of the Hebrew
Rehabilitation Center for Aged, and all subjects provided informed
consent.
Instrumentation
While lying supine at rest on a tilt table, electrodes were attached to
the chest for continuous recording of the ECG signal. The right
arm was kept level with the right atrium at all times during the study,
and a noninvasive tonometric arterial pressure (BP)
transducer, connected to a Colin Electronics BP monitor was strapped
over the right radial artery. The sphygmomanometric cuff of an
oscillometric BP recording device, used for internal
calibration of the Colin monitor, was attached to the upper right
arm.
A continuous respiration signal was recorded by an inductive
plethysmograph (Respitrace, Ambulatory Monitoring) from two elastic
respiratory transducer bands, one around the mid chest and the other
around the abdomen. The Respitrace output was calibrated according to
the procedure of Sackner et al8 by having
subjects exhale and inhale to fill and empty an 800 mL spirometer bag.
Minute ventilation (respiratory rate times average tidal volume) was
calculated during 3 minutes of spontaneous breathing during supine rest
and was subsequently held constant during periods of paced breathing by
having the subject adjust his or her depth of respiratory excursion
according to a marker on an oscilloscope screen. During paced
breathing, respiratory frequency was controlled by having subjects
follow a tape-recorded auditory signal and line on the oscilloscope
screen.
Experimental Protocol
Data Processing
Beat-to-beat R-R intervals were determined from the R wave of the ECG,
and beat-to-beat systolic and diastolic pressures
were derived from the maximum and minimum of the arterial
pressure waveform. The continuous respiration signal was sampled at
each R wave and used to determine instantaneous lung volume. Each R-R
interval, systolic and diastolic blood pressure,
and respiratory time series was interpolated by cubic spline function
and resampled at 1 Hz to obtain equidistant time intervals. The
resampled series were analyzed with the use of complex
demodulation as described previously7 and briefly
below.
Complex Demodulation
The time dependent changes in the amplitude and frequency of the low
frequency (0.04 to 0.15 Hz) and high frequency (0.15 to 0.45 Hz)
components of respiration, R-R interval, and blood pressure were
assessed on a personal computer with a subroutine CDM written in
FORTRAN (the detailed code has been deposited with the National
Auxiliary Publications Service). For the analyses of the low
and high frequency components of these variables, reference
frequencies were set at 0.095 Hz and 0.30 Hz. The low pass filtering
was performed with a zero-phase-shift least-squares filter with
convergence factors. The length of the filter was set at 61 terms,
resulting in a transitional band width of 0.033 Hz. The low-pass corner
frequencies were set at 0.055 and 0.15 Hz for the low and high
frequency components so that the frequency bands for demodulating these
components were 0.04 to 0.15 Hz and 0.15 to 0.45 Hz, respectively.
It is important to note that the respiratory amplitudes obtained with
the use of complex demodulation are relative measures of tidal volume
rather than absolute lung volumes. This is due to several factors,
including the following: (1) the amplitude computed by complex
demodulation is half the range of the respiratory signal excursion; (2)
the signal is not exactly sinusoidal, especially when expiration is
longer than inspiration or brief periods of apnea occur between
breaths; and (3) average tidal volume within a given period of
analysis represents the sum of high and low frequency
breaths, whereas complex demodulation, by definition, separates out the
amplitudes at each frequency.
Statistical Analysis
To determine whether there was a relation, and if so, the strength of
that relation between respiratory (input signal) and R-R interval
(output) fluctuations, in the low (0.04 to 0.15 Hz) and high (0.15 to
0.45 Hz) frequency ranges during upright tilt, we calculated the
coherence, transfer magnitudes, and phase relations between the signals
by using the technique of Saul et al.10 11
Coherence was calculated from the cross-spectra and autospectra of
256-second stationary data segments over 2 time intervals before the
end of tilt; 90 to 346 seconds, and 344 to 600 seconds. The following
formula was used:
Coherence=(cross-spectra)2/(input signal
autospectrum) x(output signal autospectrum). The signals were
considered coherent over the frequencies at which coherence values
exceeded 0.5.11 Transfer magnitudes and phases
were calculated for each subject over the frequency range meeting this
criterion. Transfer magnitudes were determined by dividing the
cross-spectrum by the input autospectrum.
The mean changes in R-R interval and systolic and
diastolic BP for the 2 groups of subjects over 10 minutes
before the time of syncope are shown in Figure 1
Illustrative R-R interval, systolic BP, and respiratory time
series over 2 minutes before the time of syncope for 1 syncope subject
and 1 age-matched control subject are shown in Figure 2
Complex Demodulation of Cardiovascular and
Respiratory Dynamics Before Syncope
Systolic (Figure 5
Individual Changes in Respiratory Amplitude
Coherence of Respiration and R-R Interval Variabilities
Although BP fell during the last 3 minutes before syncope, there was no
significant change in low or high frequency BP amplitude during this
time period. This may be due to the counterbalancing effect of large
respiratory amplitudes on BP, thus masking the decline in low frequency
BP fluctuations (Mayer waves) that would otherwise be expected to occur
as sympathetic activity is withdrawn from the
vasculature.12 13
Several previous studies have used time and frequency domain
analyses of heart rate variability to determine whether
subjects who are prone to vasovagal syncope have an increase in
baseline vagal tone. The results of these studies are conflicting; some
show increases in heart rate variability,14
whereas others show no difference15 or
decreases16 in syncopal subjects compared with
control subjects. The advantage of complex demodulation over previous
methods is that it permits the continuous assessment of changes in
autonomic control of cardiovascular function during
dynamic conditions that precipitate syncope. Our results indicate that
baseline cardiovagal tone is not different between syncopal and
nonsyncopal subjects but that vagal tone suddenly increases just before
the fainting. Thus vasovagal syncope may not be due to an underlying
state of hypervagotonia but to the sudden onset of a vagal reflex
precipitated by preload reduction and possibly hyperventilation.
Potential Mechanisms and Effects of Hyperpnea Before
Syncope
Potential Mechanism of Dissociation Between Respiration and R-R
Interval Variability
There are several possible explanations for the dissociation between
respiration and R-R interval variability. First, high sympathetic tone
during tilt may suppress RSA until sympathetic withdrawal before
syncope12 13 allows RSA to increase. This
hypothesis is supported by the finding in rats that
noradrenaline stimulation of aqueductal gray matter
inhibits vagal-induced bradycardia.21
Furthermore, in humans, heightened ß-adrenergic activity during
exercise reduces RSA, whereas ß-blockade may enhance
it.22
A second possible explanation for the dissociation between respiratory
and R-R interval variability before syncope is that hyperventilation
may suppress RSA. Hyperventilation abolishes the bradycardia induced by
electrical stimulation of the carotid sinus nerve in
dogs.17 By augmenting central inspiratory drive
and increasing the activity of pulmonary stretch receptors,
hyperventilation reduces the excitability of cardiac vagal
motoneurons.17 The decoupling of respiration and
RSA during hyperventilation may permit respiratory pumping without
inspiratory cardiac slowing, thereby partially counteracting preload
reduction during head-up tilt.
Third, it is possible that the increase in respiratory tidal volume did
not produce a detectable change in RSA until it reached a critical
threshold. Eckberg5 has shown that a 50%
increase in tidal volume increases the average R-R interval amplitude
by only 15%. Data from Hirsh and Bishop18
suggest that changes of <1 L in tidal volume at respiratory
frequencies >0.15 Hz have relatively little effect on RSA (<5 bpm).
Therefore we may not be able to detect changes in RSA until tidal
volume increases substantially.
Finally, it is possible that during baroreflex suppression of vagal
outflow in response to head-up tilt, respiratory gating has a minimal
effect on cardiac vagal motoneuron activity. Saul et
al10 showed that the transfer magnitude of
respiration to heart rate is lower during upright posture compared with
supine posture. Therefore respiratory and cardiac interval
oscillations could be relatively independent of one another
until vagal tone increases before syncope. This possibility requires
further study.
Limitations
In otherwise healthy subjects, tilt-induced vasovagal syncope appears
to be preceded by a period of hyperpnea that is followed by an abrupt
increase in cardiovagal tone. Whether prevention of the hyperpneic
response will prevent the development of syncope requires further
investigation.
Received January 5, 1998;
revision received March 25, 1998;
accepted April 22, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Complex Demodulation of Cardiorespiratory Dynamics Preceding Vasovagal Syncope
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—The dynamic autonomic
processes leading to vasovagal syncope are poorly understood.
Key Words: respiration • heart rate • Fourier analysis
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Vasovagal syncope is
a common and potentially dangerous clinical problem that can be
provoked by passive head-up tilt. Although previous investigations have
focussed primarily on cardiac and vascular responses preceding
vasovagal syncope, changes in breathing patterns may also occur before
fainting. Subjects have been observed to yawn, sigh, or hyperventilate
before syncope,1 2 suggesting that alterations in
respiration may accompany sudden changes in autonomic control of the
heart and vasculature. In a previous study,3 we
demonstrated vasomotor instability preceding syncope and showed that it
is probably not related to respiration. However, to our knowledge, the
relation between respiration and cardiovagal activity in neurally
mediated syncope has not been previously investigated.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Subjects
The subjects included 50 healthy volunteers (age range 20 to 64,
mean age±SD=45±20, 29 women and 21 men) who underwent passive head-up
tilt tests as described below. Twenty-five of the subjects who
developed syncope or presyncope during head-up tilt were matched to 25
who remained asymptomatic during the procedure. Subjects
with and those without syncope were matched by age to control for
age-related differences in respiratory sinus arrhythmia. All
but 3 subjects were also matched by sex. The subjects were recruited
from the local community through newspaper advertisements and the
Harvard Cooperative Program on Aging subject registry. They were
carefully screened with a medical history, physical examination,
complete blood count, chemistry screen, lipid profile, ECG, and, if
they were more than 40 years of age, a graded exercise stress test was
performed. Potential subjects were excluded if they had evidence of
cardiovascular or other diseases, smoked tobacco
products, drank alcohol, took medications other than oral
contraceptives, or were obese (body mass index >30
kg/m2) or hypertensive (systolic blood
pressure [BP] >140). None of the subjects had experienced
spontaneous syncope within the past 5 years.
Subjects reported to the Cardiovascular Research
Laboratory at the Hebrew Rehabilitation Center for Aged at 7:30 on the
morning of the study in the fasting state, after an overnight rest.
Premenopausal women were studied between days 7 and 14 of their
menstrual cycle.
After equipment attachment and calibration, subjects rested
supine for 30 minutes to reach equilibrium. Continuous ECG, BP, and
respiratory (instantaneous lung volume) data were then collected during
30 minutes of supine rest and 45 minutes of 60 degree head-up tilt. For
a period of 8 minutes between 5 and 15 minutes after the initiation of
tilt, subjects were instructed to breathe at a fixed rate of 15 breaths
per minute (0.25 Hz), as described above. While in the upright
position, subjects were carefully observed and questioned for signs and
symptoms such as dizziness, nausea, sweating, other discomfort,
yawning, or near syncope. If subjects became symptomatic or
hypotensive (systolic BP <80 mm Hg) during tilt,
they were returned immediately to the supine position. The tilt was
usually terminated before actual loss of consciousness occurred.
All data were digitized at 250 Hz and displayed in real time
with the use of commercially available data acquisition software
(Windaq, Dataq Instruments) on a personal computer. Continuous ECG and
BP data before and during tilt were visually inspected and edited
off-line for artifact and ectopy with the use of an automated
arrhythmia detection program for the ECG and manual editing for
BP. Five to 10 minute data segments during tilt were used for
analysis. These included intervals during paced breathing and
spontaneous breathing just before syncope or at the same time points
coinciding with the presyncopal period in matched nonsyncopal control
subjects. The presyncopal segments were at least 5 minutes long and did
not overlap with paced breathing. For each matched control subject, the
same length data segment was analyzed.
Complex demodulation is a nonlinear time-domain method of time
series analysis suited to investigation of
nonstationary/unstable oscillations.7
In contrast to spectral analysis that provides average
properties (power and frequency) of oscillatory components in
stationary time series, complex demodulation provides instantaneous
amplitude and frequency as a function of time for
oscillations in a frequency band of interest.
Within-group changes in raw values, frequencies, and amplitudes
for each cardiovascular signal were evaluated over time
with repeated-measures ANOVA. To determine the times at which changes
occurred before syncope, we contrasted each point during the last 5
minutes of tilt to the mean of the preceding 5-minute period.
Between-group differences in each signal were assessed by Student's
t tests and a general linear model, repeated-measures ANOVA
with interaction terms. To determine individual time points at which
differences were significant, the Helmert transformation was used. All
analyses were performed with SAS software on a personal
computer.9 Data are expressed as mean
values±SE.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Cardiovascular Responses Before Syncope
There were no significant group differences in subject ages, or
their average systolic and diastolic BPs, interbeat
intervals, tidal volumes, and corresponding spectral powers during
paced or spontaneous breathing under pretilt and initial tilt (first 15
minutes) conditions. The 25 subjects with syncope developed pallor,
diaphoresis, dizziness and/or transient loss of consciousness within 17
to 40 minutes of head-up tilt. Blood pressure began to fall at the time
symptoms developed, and relative bradycardia followed. The tilt was
terminated when systolic BP fell below 80 mm Hg. All
subjects recovered spontaneously on return to the supine position. 
. If the tilt was terminated before a
full 10 minutes of spontaneous breathing data could be obtained,
shorter segments (at least 5 minutes) were analyzed for both
the syncope subject and their matched control subject and are included
in Figure 1. There were no significant differences in R-R interval, or
systolic and diastolic BP between the groups until
approximately 3.5 minutes before the end of tilt. In the syncope group,
systolic and diastolic BP began to fall at 210
seconds and R-R interval began to increase at 90 seconds before the end
of tilt. There was a small change in R-R interval during the same time
period in nonsyncopal subjects, but this was significantly smaller than
the change in syncopal subjects (P=0.0001, time by group
interaction). There were no significant changes in BP in the nonsyncope
group.
View larger version (29K):
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Figure 1. Time dependent changes in R-R interval (top),
systolic BP (middle), and diastolic BP (bottom) in
syncope subjects ( 
) and nonsyncopal control subjects (
) during 10
minutes preceding time of syncope. If subjects developed syncope or
presyncope before full 10 minutes of spontaneous breathing data could
be obtained, shorter segments (
5 minutes) are included in the graph
for both them and their matched control subject. #Statistically
significant within-group changes over time (P<0.05 by
repeated-measures ANOVA); *time points that differ significantly from
mean of first 5-minute period (P<0.05 by Helmert
transformation). Significant time by group interactions are shown in
each panel.. Note the large respiratory amplitude
in the syncope subject compared with the control subject as BP fell
before syncope. This subject also had large fluctuations in
systolic BP that appeared to coincide with respiratory
oscillations. However, these systolic BP
fluctuations were not significantly greater among the group of syncope
patients than among the control subjects.
View larger version (25K):
[in a new window]
Figure 2. Illustrative R-R interval (top), systolic
BP (middle), and respiratory (bottom) time series over 2 minutes before
time of syncope for one 34-year-old male syncope subject and one
35-year-old male control subject.
Complex demodulation of cardiovascular and
respiratory dynamics before syncope assessed the changes in frequencies
and amplitudes in the high and low frequency bands for respiration
(Figure 3), R-R interval (Figure 4), and systolic BP (Figure 5) during the 10 minutes before the time
of syncope for both groups of subjects. In syncope patients, the
respiratory amplitude in both high and low frequency bands began to
increase significantly at 180 seconds before the onset of syncope
(Figure 3). This was due to greater volumes of rapid (high frequency)
shallow breaths as well as slower (low frequency) cycles of deeper
breaths. The amplitude of R-R interval variability in the low frequency
band did not change significantly until immediately before syncope
(Figure 4). The amplitude of R-R interval variability in the high
frequency band began to increase 90 seconds before terminating the tilt
(Figure 4), the same time at which bradycardia began to develop (Figure 1
). The amplitudes of respiration and R-R interval did not change in
either frequency band during matched time periods in the nonsyncopal
control subjects. There were no significant changes in the frequency
within the low and high frequency bands of respiration or R-R interval
before the time of syncope for either group.
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Figure 3. Respiratory low frequency frequency (Resp LFF,
top), respiratory low frequency amplitude (Resp LFA, second from top),
respiratory high frequency frequency (Resp HFF, second from bottom),
and respiratory high frequency amplitude (Resp HFA, bottom) in syncope
subjects ( ) and nonsyncopal control subjects () during 10 minutes
preceding time of syncope. If subjects developed syncope or presyncope
before full 10 minutes of spontaneous breathing data could be obtained,
shorter segments (5 minutes) are included in graph for both them and
their matched control subject. #Statistically significant within-group
changes over time (P<0.05 by repeated-measures ANOVA);
*time points that differ significantly from mean of first 5-minute
period (P<0.05 by Helmert transformation). Significant
time by group interactions are shown in each panel.
View larger version (28K):
[in a new window]
Figure 4. R-R interval low frequency frequency (RRI LFF,
top), R-R interval low frequency amplitude (RRI LFA, second from top),
R-R interval high frequency frequency (RRI HFF, second from bottom),
and R-R interval high frequency amplitude (RRI HFA, bottom) in syncope
subjects ( ) and nonsyncopal control subjects () during 10 minutes
preceding time of syncope. #Statistically significant within-group
changes over time (P<0.05 by repeated-measures ANOVA);
*time points that differ significantly from mean of first 5-minute
period (P<0.05 by Helmert transformation). Significant
time by group interactions are shown in each panel.
View larger version (28K):
[in a new window]
Figure 5. Systolic BP low frequency frequency (LFF,
top), systolic BP low frequency amplitude (LFA, second from
top), systolic BP high frequency frequency (HFF, second from
bottom), and systolic BP high frequency amplitude (HFA, bottom)
in syncope subjects ( ) and nonsyncopal control subjects () during
10 minutes preceding time of syncope. #Statistically significant
within-group changes over time (P<0.05 by
repeated-measures ANOVA).) and diastolic BP (not shown)
variabilities were similar in both groups before the time of syncope.
Although there were small changes in the frequency of systolic
and diastolic BP in the low frequency band among control
subjects, these changes were not significantly different from those in
the syncope group.
Because the mean changes in amplitude of fast and slow breaths
could be influenced by a few outliers, we also analyzed the
distributions of individual responses before the time of syncope. Using
the 5 minute period of paced breathing during early tilt as a uniform
reference for all subjects, we determined the number of subjects who
doubled or tripled the amplitude of low frequency breaths, or halved
the amplitude of high frequency breaths, during 5 minutes of
spontaneous breathing before the termination of tilt for syncopal
subjects, or during matched time periods for control subjects. As shown
in Table 1, significantly more syncope
than nonsyncope subjects at least doubled or tripled the amplitude of
low frequency (slow) breaths. Only 1 syncope subject reduced high
frequency amplitude by 50% or more compared with 10 of the control
subjects (P=0.002).
View this table:
[in a new window]
Table 1. Number of Subjects With Large Changes in Respiratory
Amplitude Before Time of Syncope
Table 2 shows the number of subjects
in each group with coherence between their respiratory and R-R interval
time series, with corresponding coherence, transfer magnitude, and
phase data over 2 time intervals: just before the time of syncope (90
to 346 seconds) and more distant (344 to 600 seconds). Fewer syncope
than nonsyncope subjects showed coherence during the 344- to 600-second
period (P=0.05). In the period just before the time of
syncope, the transfer magnitudes tended to decrease in the syncope
subjects and became significantly lower compared with nonsyncopal
control subjects (P=0.003). The phase relation between the
two signals was consistently negative, indicating that
respiration led R-R interval changes.
View this table:
[in a new window]
Table 2. Coherence, Transfer Magnitudes, and Phase Between
Respiration (Instantaneous Lung Volume) and R-R Interval
Variabilities
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Principal Findings
The principal results of this study are as follows: (1) Healthy
subjects with tilt-induced vasovagal syncope experience increases in
respiratory amplitude beginning 3 minutes before systolic BP
reaches 80 mm Hg and syncope is imminent. The increase in
respiratory amplitude begins at the time that blood pressure begins to
fall. Because respiratory frequency remains unchanged during this time
period, the subjects are probably hyperventilating. (2) At
approximately 90 seconds before syncope there is a sudden prolongation
of R-R interval and increase in high and low frequency R-R interval
amplitude that indicates an abrupt enhancement of vagal tone. (3) The
increase in respiratory amplitude between 180 and 90 seconds before
syncope is not accompanied by changes in R-R interval or R-R interval
variability, suggesting there is dissociation between respiration and
the vagally-mediated "respiratory sinus arrhythmia." This
finding is reinforced by the coherence analysis, which showed
fewer syncope subjects with coherence between respiratory and R-R
interval variabilities before the end of tilt and lower transfer
magnitudes in syncope subjects compared with control subjects during
this time period.
Although hyperpnea has been observed in individual patients before
syncope1 2 and is popularly known to produce
syncope when used in combination with the Valsalva maneuver, it has not
been widely recognized as a typical physiological
response preceding a vasovagal faint. Hyperpnea may be a primary or
secondary event. It may result from autonomic outflow to the lungs from
brain centers that are stimulated at the onset of vasovagal syncope.
Or, it may be a secondary response to the vasodilatation and
hypotension that also precedes syncope. Hyperpnea can generate large
negative intrathoracic pressures that may act as a "respiratory
pump" to enhance venous return. This may account for the large
respiratory and BP fluctuations seen in the syncope patient shown in
Figure 2. The respiratory pump might prevent syncope unless such large
pressures are generated that intrathoracic veins actually
collapse.17 Although large intrathoracic
pressures might explain the sudden cardiovascular
collapse that occurred when respiratory amplitude reached its peak, it
is unlikely that sufficiently large pressures were generated to produce
syncope. Alternatively, a respiratory alkalosis associated with
hyperventilation may cause cerebral vasoconstriction. The consequent
reduction in cerebral blood flow could predispose to the development of
syncope. Unfortunately, we were unable to measure pH,
PCO2, or cerebral blood flow during
the study.
Respiration is usually closely coupled to heart rate, producing
the respiratory sinus arrhythmia (RSA). However, our data
suggest that respiratory and cardiac interval oscillations
can also occur independently. During conditions when vagal tone remains
constant, increases in tidal volume have been shown to increase the
amplitude of the RSA.5 18 19 20 Our results during
the 5 minutes before the time of syncope show that respiratory
amplitude increases for at least 1.5 minutes before there is any change
in R-R interval variability. Furthermore, during this increase in
respiratory amplitude the transfer magnitude between respiration and
R-R interval is low. When vagal tone later increases, as is evident by
an increase in R-R interval just before syncope, the amplitude of RSA
also increases, along with further increases in respiratory amplitude.
It is not clear whether respiration becomes coupled with cardiovagal
activity at this point or whether these two systems continue to operate
relatively independently.
There are several limitations to this study. First, we were unable
to measure sympathetic nervous system activity directly and therefore
do not know whether high sympathetic tone suppressed the respiratory
sinus arrhythmia or whether a sudden reduction in sympathetic
tone preceded syncope. Also, because we did not measure
arterial PCO2 and pH, we
cannot confirm the presence of hyperventilation or whether
hyperventilation produced a respiratory alkalosis and associated
hemodynamic collapse. Although the primary study
variables (respiration, R-R interval, and BP) were the same for
both groups until 3.5 minutes before the end of tilt, the absence of
other hemodynamic measurements makes it difficult to
know for sure whether the two study groups experienced the same
orthostatic stress. Because the resolution of complex
demodulation is approximately 30 seconds, we cannot ascertain the exact
timing of autonomic changes before syncope. Nevertheless, complex
demodulation enabled us to identify distinct changes in respiratory and
cardiac interval dynamics before syncope that previous studies have
been unable to address. Finally, we studied healthy subjects with no
recent history of spontaneous syncope. Therefore our findings may not
be generalizable to patients who are seen by physicians for the
evaluation of spontaneous syncope.
Acknowledgments
This study was supported by US Public Health Service grant
AG04390 from the National Institute on Aging, Bethesda, Md, a
Short-Term Visiting Scholarship Grant from Nagoya City University to Dr
Lipsitz, and a Research Grant for Aging and Health from the Japanese
Ministry of Health and Welfare to Dr Hayano. Dr Lipsitz holds the
Irving and Edyth S. Usen Chair in Geriatric Medicine at the Hebrew
Rehabilitation Center for Aged.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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N. D. Giardino, R. W. Glenny, S. Borson, and L. Chan Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1585 - H1591. [Abstract] [Full Text] [PDF]
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