Review Article

Respiration And Heart Rate Variability : A Review

With Special Reference To Its Application In Aerospace Medicine
Lt Col KK Tripathi*

ABSTRACT
Heart Rate Variability (HRV) indices provide a non-invasive assessment of cardiovascular control mechanisms.
The last few years have witnessed a burgeoning growth of research effort and literature on various HRV indices,
encompassing a large cross section of cardiovascular and autonomic physiology/psychophysiology. The analysis
finds varied applications in a multitude of fields including Aerospace Medicine. After presenting a brief summary
of linear and nonlinear HRV indices, the present article reviews the effects of various respiratory influences on
different HRV estimates with the mechanisms involved therein. Certain examples are given, from the field of
Aerospace Medicine, of the application of HRV analysis wherein respiration could be a potential confounder.
Concerns expressed regarding effects of controlling the respiratory variables on HRV indices are addressed and,
finally, the issue of susceptibility of non-linear HRV estimates to breathing is dealt with.
IJASM 2004; 48(1): 64-75
Keywords :Heart rate variability, Spectral analysis, Sympatho-vagal balance, Entropy

I n the recent past, there has been a spurt of research

efforts involving heart rate variability (HRV) which
provides a non-invasive assessment of cardiovascular
mean of the 5-min standard deviation of the NN interval
calculated over 24 hours measuring the variability due to
cycles shorter than 5 min. The most commonly used
control mechanisms. A search, made in PubMed, returns measures derived from interval differences include
more than 4,000 citations. Both linear and nonlinear HRV RMSSD, the square root of the mean squared differences
measures have been used. Mostly, the HRV is measured of successive NN intervals, NN50, the number of interval
using linear estimates which include various time and differences of successive NN intervals greater than 50
frequency domain indices. However, a few non-linear ms, and pNN50, the proportion derived by dividing NN50
indices of HRV have also been proposed. by the total number of NN intervals [1].

Linear measures of HRV Frequency domain indices provide information on

both total variability as well as its distribution as a function
Linear measures of HRV include various time and
of frequency. Various spectral methods are available.
frequency domain indices. Time domain indices provide
Spectral analysis of RR intervals derived from short term
information on total variability over a period of time recordings of 2 to 5 min yields three separate bands -
(without resolving it further).

(a) A very low frequency (VLF) band located in the

The time domain indices could be derived from less than 0.04 Hz (with dubious physiologic
direct measurements of the RR intervals (or significance).
instantaneous heart rate) or from the differences between
RR intervals. The former include SDNN (standard (b) A low frequency (LF) band located in the 0.04-0.15
Hz range (which derives from short term regulation
deviation of the normal to normal interval ie, the square
of blood pressure).
root of variance), SDANN (standard deviation of the
average NN interval calculated over short periods, usually * Associate Professor & Classified Specialist in
5 min and is an estimate of the changes in heart rate due Aviation Medicine, IAM, IAF, Vimanapura PO,
to cycles longer than 5 min) and the SDNN index, the Bangalore – 560 017

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 Respiration And Heart Rate Variability : Lt Col KK Tripathi

(c) A high frequency (HF) band with a very large range Hurst exponent ‘H’ and Detrended Fluctuation Aanalysis
from 0.15-0.50 Hz (reflecting momentary respiratory (DFA). In 1/f scaling, the slope ß of the power spectrum
influences on the heart rate or respiratory sinus is calculated by a regression analysis of log(power) and
arrhythmia) [1]. log(frequency) plots of the smoothed power spectrum
usually over the frequency range of 10-2 to 10-4 Hz. Hurst
The HF component is decreased by tilting or
exponent is a measure of the smoothness of fractal time
parasympathetic blocking drugs and is increased by
series based on the asymptotic behaviour of the rescaled
sympathetic blocking drugs [2,3]. Therefore, the HF
range of the process. DFA of heart rate variability was
component is thought to provide a quantitative and
initially presented as a specialised time-domain
specific index of vagal cardiac function. On the other
technique, in which the series of RR intervals undergoes
hand, the LF component is increased while standing and
cumulative summing and then segmentation into short
the increase is blocked by intravenous propranolol [2,3].
segments. Within each segment, the degree of dispersion
Moreover, this component is not found in quadriplegic
of the cumulated time series away from its linear trend is
humans who have severe dysfunction of the sympathetic
measured (as the sum of squares of residuals after
nervous system [4]. Therefore, the LF component in
subtracting the linear regression line). The total of the
humans has been interpreted as an indicator mainly of
squared residuals for the individual segments is
sympathetic influence. Consequently, the LF/HF ratio is
calculated for the overall data set. The entire process is
considered to be a convenient index of sympatho-vagal
then repeated with a different segment length. As the
interaction.
segments become longer, the degree of dispersion away
from the linear regression lines within the segments tends
Nevertheless, interpretation of LF components is to increase. The rate at which this total dispersion
controversial. It is considered by some (vide supra) as a increases as the segments become longer is measured
marker of sympathetic modulation (especially when as a slope (a) on a log–log plot over particular regions of
expressed in normalised units) and by others as a segment length, eg, 4–16 beats or 16–64 beats. As a
parameter that includes both sympathetic and matter of fact, it is the range used, originally, by Ho et al
parasympathetic influences [5]. [6]. Steeper slopes are said to show higher complexity.

Nonlinear measures of HRV The above three indices are related to each other
There is some evidence for the involvement of as follows -
nonlinear phenomena in the genesis of HRV. It is
conceived that assessment of HRV with nonlinear ß =2H+1 and ß=2a-1
measures may supply information different from and
additional to that derived through linear measures.
Another approach to nonlinear measures of HRV
Different approaches have been employed for the
is the quantification of complexity from the point of view
nonlinear analysis of HRV. In nonlinear dynamics theory,
of information theory. The sequence of heart periods
the so-called state space is reconstructed from sequences
can be analyzed with the help of entropy measures such
of heartbeat periods which are generally defined as the
as Shannon entropy or renormalized entropy. These are
time duration between successive R waves.
often used in conjunction with the concept of symbolic
Subsequently, the state space and the dynamic behaviour
dynamics or coding theory, ie, reducing the amount of
of the reconstructed dynamics can be quantified (eg, with
information by transforming the original time series into
measures of dimension or Lyapunov exponents).
a symbolic sequence with a small set of symbols. The
concept of entropy, as it applies to signals like R-R
Since evolution in time of HRV signal shows self intervals, is to quantify the repetition of patterns in that
similarity properties, certain methods are based on fractal signal. Larger values of entropy correspond to greater
analysis. These include- 1/f scaling of Fourier spectra, apparent randomness or irregularity, whereas smaller

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Respiration And Heart Rate Variability : Lt Col KK Tripathi

values correspond to more instances of recognizable with the mechanisms involved. Certain examples are
patterns in the data. Another entropy measure for given, from the field of Aerospace Medicine, of the
quantification of regularity in a time series is the application of HRV analysis wherein respiration could
approximate entropy (ApEn). ApEn(m, r, n) is be a potential confounder. Concerns expressed regarding
approximately equal to the negative average natural effects of controlling the respiratory variables on HRV
logarithm of the conditional probability that two indices are addressed in the subsequent section. Since
sequences that are similar for ‘m’ data points remain all the above issues refer almost exclusively to the linear
similar within a tolerance ‘r’ at the next point and sample estimates, a separate account is given of the
entropy. However, ApEn has significant weaknesses, susceptibility of nonlinear HRV estimates to breathing.
notably its strong dependence on sequence length and
its poor self-consistency and certain alternatives have
What All Respiratory Parameters Could Affect The HRV
been suggested [7].
Estimates?
The respiratory parameters which can affect HRV
For data representation, Poincarè sections, low-
estimates, include- respiratory frequency (Rf) [9,10], tidal
dimension attractor plots, singular value decomposition,
volume [10], end tidal partial pressure of carbon di-oxide
and attractor trajectories have been used [1].
(PETco2) [10,11], the time ratio of expiration/inspiration
[12] and respiratory dead space [13]. Since breathing
In the field of aerospace medicine, HRV analysis through an oro-nasal mask or mouthpiece can also affect
has been employed to study such diverse stressors as breathing pattern and components of ventilatory
hyporbaric hypoxia, both micro and hypergravity and responses to chemostimuli [14], it can be extrapolated
vibration. It has also been used in a number of fields in that it will also influence HRV estimates- an observation
psychophysiology, as well. For example, HRV measures of importance in the aerospace settings.
have been investigated extensively as indices of mental
workload.
How Do The Above Respiratory Parameters Affect
HRV?
Despite such a varied and wide application of HRV,
Respiratory frequency & tidal volume
not much attention has been paid, by the researchers, to
control or factor out the confounding effects of respiration The variation of heart rate in the frequency range
on HRV indices. Brown and his associates [8], in their of respiration, known as respiratory sinus arrhythmia
review of studies reporting human R-R interval power (RSA), was already described by Ludwig in 1847 [15].
spectra, observed that only 51% of the studies controlled Despite many past studies, the precise mechanisms of
respiratory rate, 11% controlled tidal volume, and 11% respiration-induced SA are still debated. The theories
controlled both respiratory rate and tidal volume. In a which have been proposed are not mutually exclusive.
more recent review, Schipke et al [9] found that respiration The most important ones are the modulation of cardiac
was referenced in approximately 15% of the papers on filling pressure by respiratory movements [16], the direct
heart rate variability returned from a search in the Index respiratory modulation of parasympathetic and
Medicus. These observations are ironically surprising sympathetic neural activity in the brain stem [17] and the
because the respiratory influences on HRV are so protean respiratory modulation of the baroreceptor feedback
and powerful that no worthwhile interpretation can be control [18].
made of the analysis of HRV unless these respiratory
confounders are controlled. A variety of respiratory
In a recent review of published evidence, Eckberg
influences can affect HRV.
[19] summarised that respiratory fluctuations of muscle
sympathetic nerve activity and electrocardiographic R-
In the present article, a review is made of effect of R intervals result primarily from the action of a central
various respiratory influences on different HRV estimates ‘gate’ that opens during expiration and closes during

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inspiration. Parallel respiratory fluctuations of arterial anesthetized dogs, Hayano et al [24] also showed that
pressures and R-R intervals are thought to be secondary RSA reduces physiological dead space, ie, the alveolar
to arterial baroreflex physiology- changes in systolic dead space, by matching perfusion to ventilation during
pressure provoke changes in the R-R interval. However, each respiratory cycle.
growing evidence suggests that these parallel
oscillations result from the influence of respiration on
It has been shown in conscious humans [27] that
sympathetic and vagal-cardiac motoneurones rather than increase in RSA magnitude due to the direct effects of
from baroreflex physiology. CO2 are independent of changes in tidal volume and
breathing frequency.
In yet another synthesis, RSA could be a
physiologic phenomenon reflecting respiratory- Relative timing of inspiration and expiration
circulatory interactions improving the efficiency of
pulmonary gas exchange. The matched timing of alveolar Strauss-Blasche et al [12] showed that RSA can
ventilation and its perfusion with RSA within each also be modulated by a third respiratory variable. In their
respiratory cycle could save energy expenditure by experiment, examining the effect of a variation in
suppressing unnecessary heartbeats during expiration inspiration and expiration times on heart rate variability,
and ineffective ventilation during the ebb of perfusion the subjects were given 2 x two min trials of controlled
(vide infra). breathing with either short inspiration followed by long
expiration or long inspiration followed by short expiration.
Average expiration/inspiration time ratios were 1.0 and
Change in end tidal PCO2 3.4, respectively and the respiration rate in both trials
The most likely mechanism responsible for was approximately 10 cycles/min. In trials with short
increased RSA magnitude, with an increase in PETco2, is inspiration followed by long expiration, RSA (measured
chemostimulation that enhances respiratory modulation by mean absolute differences and by the high frequency
of vagal outflow. Stimulation of carotid chemoreceptors band) was significantly larger than in trials with long
by increased arterial Pco2 has primarily an excitatory effect inspiration followed by short expiration. This effect could
on vagal preganglionic neurons to the heart in the not be accounted for by differences in respiratory rate or
expiratory phase [20,21]. In unanesthetized trained dogs, amplitude. The higher RSA during fast/slow respiration
Yasuma and Hayano [22] reported that hypercapnia is primarily due to a more pronounced phasic heart rate
(PETco2 up to 54 mmHg) increases RSA magnitude by increase during inspiration, indicating that inspiratory
62% with no concomitant changes in mean R-R interval. vagal blockade is sensitive to the steepness of inspiration.

Increased RSA could also be a manifestation of Cardiac aliasing

cardiorespiratory interactions [23] which contribute to There is yet another mechanism reported to be
CO2 elimination by reducing physiological dead space involved in mediating respiratory fluctuations of heart
and intrapulmonary shunt, ie, matching the distribution beat. Witte et al [28] observed that if a special
of pulmonary blood flow to lung volume during each relationship exists between mean heart rate (fHR) and
respiratory cycle [24]. An increased demand for CO2 mean frequency of breathing (fB) such that fB is greater
elimination may therefore enhance RSA to facilitate than 1/2 fHR, RSA can be observed in a frequency range
pulmonary gas exchange. Regulation of RSA magnitude which is lower than the frequency of breathing. The
by PaCO2 could complement CO2-modulated changes in mathematical fundamentals of this physiological
airway smooth muscle tone in controlling dead space. phenomenon are the same as those for the ‘aliasing’
Hypercapnia is shown to both decrease tracheal diameter effect in signal sampling. The authors termed it ‘cardiac
in anesthetized dogs [25] and causes aliasing’ and could experimentally demonstrate it in
bronchoconstriction in decerebrate cats [26]. In adult rabbits and dogs as well as in human neonates.

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Respiratory dead space respiration rates. LF power differed up to 72%, HF power

up to 36% and R up to 48%. These results show that
Hirsch JA and Bishop B [14] demonstrated that
respiration can change HRV power spectra both in high
choice of a mouthpiece or a face mask can differentially
and low frequency regions (Figure-1, drawn from the
change breathing pattern and all the components of
ventilatory responses to chemostimuli. These breathing data presented by Schipke et al, refers).
Fig-1
apparatus effects did not appear to be a simple BREATHING FREQUENCY & SPECTRAL HRV POWER
consequence of a shift from oronasal to oral breathing. [Drawn from the data of Schipke et al, 1999]

In an interesting study, Furutani Y [13] evaluated the 1000

effect of the dead space induced by the face mask used

800
in the expiratory gas exchange analysis on the
measurement of heart rate variability using ECG records

Power (ms2)
600

for 5 min during spontaneous respiration under the

400
conditions of supine rest, sitting on the bicycle ergometer
with and without a face mask. The value of LF/HF 200

increased from supine rest to sitting in accordance to 0

the change of body position, but the value of LF/HF 0.00 0.10 0.20 0.30 0.40 0.50
Breathing Frequency (Hz)
when sitting with the face mask decreased to the level Heart rate remained unchanged throughout the protocol

LF Power (0.05-0.15 Hz) HF Power (0.15-0.45 Hz)

during supine rest. The value of HF/TP decreased from
Novak [29] studied the dynamics of the respiratory
supine rest to sitting, but when sitting with the face mask
and cardiovascular systems by continuously slowing
returned to that during supine rest. It was also seen that
respiration from 0.46 to 0.05 Hz. During rest, the
the value of LF/HF decreased from supine rest to sitting
with the face mask in the smaller tidal volume group (tidal nonrespiratory-to-respiratory frequency ratios were not
volume<570 ml) and there was a significant correlation affected by occasional slow breathing. As respiration
between the change of the value of LF from supine rest slowed to 0.07-0.09 Hz, the frequency content of the
to sitting with the face mask and the tidal volume. These respiration and cardiovascular variables increased
results suggest that the power spectrum of heart rate sharply and nonlinearly to a maximum that exceeded
variability is strongly influenced by the dead space values at higher frequencies. The nonrespiratory
induced by the face mask used in expiratory gas exchange frequency content remained stable in the 0.01- to 0.05-Hz
analysis. Even though the sympathetic activation from range and did not significantly differ from that at rest. In
supine rest to sitting in subjects with the smaller tidal contrast, the 0.05- to 0.1-Hz component was suppressed.
volume is unclear, interpretation of the results of heart A slow 0.012- to 0.017-Hz rhythm modulated respiration
rate variability with or without the face mask used requires and hemodynamic fluctuations at both respiratory and
care. nonrespiratory frequencies. The study indicated that
respiration input should be considered in the
interpretation of global spectra.
Is Respiratory Influence Confined To Only High
(Respiratory) Frequencies In The HRV Power
Spectrum? However, recently, independence of low-frequency
rhythms from respiratory activity is reported [30].
Schipke et al [9] examined the effect of controlled
respiration at six different breathing frequencies on HRV
indices derived from short term recordings of six minutes Sasano [27] failed to observe any change in low
each. Breathing frequencies ranged from below the low- frequency power or LF/HF ratio over a range of PETco2
frequency range (LF) of the power spectrum (0.03 Hz) to (30, 40 & 50 mm Hg) in conscious human subjects despite
above HF (0.50 Hz). Heart rate remained unchanged a significant increase in RSA. Mean R-R interval did not
throughout the protocol, indicating a steady differ at PETco2 of 40 and 50 mmHg but was less at 30
haemodynamic state. HRV differed up to 33% in SDNN, mmHg and changes in tidal volume and breathing
37% in RMSSD and 75% in pNN50 between the different frequency were prevented.

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Even if low frequency region of HRV power spectra studies failed to observe bradycardia under normoxic
is relatively insusceptible from the respiratory influences, conditions in unanesthetized rats despite similar density,
the latter will affect interpretation of spectral values in pressure, and inert gas components.
low frequency region in normalised terms due to a
significant change in the total power.
A decrease in the resting muscle sympathetic nerve
activity (MSNA) is observed in human volunteers
Certain Examples From Aerospace Settings Wherein exposed to hyperbaric conditions [41]. Normobaric
HRV Estimates Could Be Confounded From Respiratory hyperoxia (100% O2 at sea level) also lowers heart rate
Influences and MSNA at rest [42,43].

Hypoxia
These observations lend support to hypothesis
Assessment of autonomic function during
that hyperoxia attenuates sympathetic nerve activity.
exposures to hypoxia is important as the former may
However, bradycardia in normobaric hyperoxia remains
affect tolerance to this stress and could contribute to
unaffected in dogs by ß-adrenoceptor blockade but is
certain specific syndromes viz, acute mountain sickness,
completely prevented by cholinergic blockade [44]. It is
high altitude pulmonary edema, and high altitude cerebral prevented by intramuscular administration of atropine
edema. HRV analysis has generally shown an increase in [45]. These observation suggest that bradycardia in
cardiac sympathetic activity after acute exposure to normobaric hyperoxia could be mediated through
hypoxia [31, 32, 33] without a significant change in the parasympathetics.
fractal component (which indicated overall ‘irregularity’
of HRV). Certain studies have, however, reported results
which are not in consonance with the above To further complicate the matter, substantial
observations. For example, Sevre et al [34] have shown a degrees of bradycardia have also been observed in
transient reduction in both parasympathetic and humans during hyperbaric exposure with normoxic or
near-normoxic gas mixtures [46]. The non-O2-dependent
sympathetic activity during stepwise exposure to high
bradycardia, thus, must be caused by other factors, such
altitude. Pre-adaptation to hypoxia is shown to modulate
as the increased hydrostatic pressure, the increased gas
HRV responses in rats [35] but not in humans [31]; this
density, or the increased partial pressure of metabolically
difference could be due to difference in the period of
inert gas(es) alone or in combination. Other contributing
acclimatisation. HRV analysis has also been used to
factors could be the thermal conductivity of the ambient
demonstrate ethnic variations in reactions to hypoxia
gas and of the breathing gas, especially if these gases
[36] and assessment of baroreflex responsiveness in
include helium (He) [47].
hypoxia [34]. In almost all the above studies, the results
are not without confounding effects of one or more
respiratory variables (viz breathing frequency, tidal Therefore, a multitude of efforts have been made,
volume, PETco2, dead space etc) which were neither using analysis of HRV, to explore the precise behaviour
controlled nor monitored. All these respiratory attributes of and interplay between sympathetic and
are known to change during hypoxia [37,38]. parasympathetic branches of ANS in hyperbaric
hyperoxia. These studies have yielded conflicting results
[48-51]. One possible reason for the conflicting results
Hyperbaria with/without hyperoxia from the above studies could be the confounding effect
Bradycardia has been observed in animals and of respiratory variables which were neither controlled
humans upon exposure to various hyperbaric nor monitored. Other confounding variables could have
environments. Because of the complexity of the been hypoventilation and carbon di-oxide retention [46]
hyperbaric environment, the cause of the bradycardia is which are often reported during hyperbaric exposure.
not obvious. Certain investigators [39, 40] have Moreover, most of the above studies used professional
concluded that hyperoxia is the most important variable divers as subjects with reduced adrenergic and stress
in the development of hyperbaric bradycardia as these response to CO2 [52].

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Tilt table & LBNP studies Hypergravic simulations

A progressive decrease in end tidal PETco2 may McKenzie [56] investigated the effect of simulated
occur during tilt due to relative hyperventilation. Whether increases in gravity (G) force on blood pressure and heart
control of breathing will help arrive at a different rate variability in seven normal healthy subjects using a
interpretation about autonomic function is controversial. man-carrying centrifuge. Subjects were exposed to 3.6
Certain investigators have used a controlled breathing Gz forces while breathing at a fixed rate and depth.
protocol during such studies [53]. On the other hand, Increases in G force produced increases in spectral power
some studies have shown that both physiologic reactions of systolic blood pressure and diastolic blood pressure
and outcome of a tilt table study may be significantly at the respiratory frequency (0.2 Hz) and less conspicuous
affected by paced breathing [54]. Others [55] observed but significant increases in spectral power at lower
that it may be possible to arrive at similar interpretation frequencies (0.045-0.15 Hz). The spectral power of beat-
about autonomic function with and without using control to-beat interval did not change. Author postulated that
of respiratory rate. Figure-2, derived from the data of this the reduction in central blood volume produced by
study, refers. increased gravity is affecting blood pressure control in a
similar way to that seen in hypovolaemic animals. The
LF
marked increase in blood pressure fluctuations induced
1.00
LBNP Tilt
by respiration at the higher G levels was viewed as a
LBNP
0.80 Tilt result of the alteration in venous return to the right atrium,
0.60 ultimately reflected as fluctuating left ventricular output
Power (nu)

Supine and pressure.

0.40 Supine

0.20
Contrary to this, Pipraiya [57] observed a significant
0.00 reduction in total (0.04-0.40 Hz) as well as HF (0.15-0.40
Spontaneous Controlled
Hz) power in absolute terms during centrifugation of
HF human subjects at +3Gz for 1 minute. Change (an
0.50 increase) in LF (0.04-0.15 Hz) power was found to be
0.40 Supine
significant only when normalised to total power.
Additionally, he observed a leftward shift of the ‘peak
0.30 Supine
power frequency’ (ie, the frequency at which maximum
Power (nu)

0.20 power was concentrated) in the LF band signifying a

Tilt change in the responsiveness of the sympathetic effector
0.10 LBNP Tilt LBNP
organs. Breathing could not be controlled but was
0.00 monitored during centrifugation. The author reasoned
Spontaneous Controlled
that a change in breathing rate from 15.7±1.3 in resting
Fig-2 sitting to 17.6±1.2 during centrifuge run was too small to
Effect Of Spontaneous & Controlled Breathing On explain the changes in spectral power.
HRV Spectral Power During Tilt and LBNP

[Drawn from data of Patwardhan et al, 2001] Assessment of baroreflex sensitivity

HRV is also employed for the non invasive
However, these results are to be viewed carefully. assessment of baroreflex sensitivity (BRS). Low-
Authors only conclude that metronomic breathing may frequency (LF) blood pressure variability (BPV) to HRV
not provide any additional insight into autonomic transfer-index is a common method for this. However,
function than what can be obtained during spontaneous this derivation assumes that all LF-HRV is caused by
breathing. The effect could simply have been because baroreflex feedback of LF-BPV. Nevertheless, respiration
the breathing frequency did not change much. may also cause HRV by mechanisms not involving the

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 Respiration And Heart Rate Variability : Lt Col KK Tripathi

baroreflex. Application of narrow-band (controlled) high- Microgravity

frequency breathing would keep such non-baroreflex-
mediated HRV best out of the LF band. On the other
HRV has been used, during and after exposure to
hand, spontaneous breathing, because of its broad-band
microgravity or its simulation, as a non invasive tool to
character, might cause extra, non-baroreflex-mediated,
monitor autonomic functions [66-71]. It has also been
HRV in the LF band, while paced LF breathing would
used to assess the efficacy of pharmacological
even concentrate most non-baroreflex-mediated HRV in
intervention in preventing the effects of increase in the
the LF band. In an interesting study, Frederiks et al [58]
effects of Epinephrine induced by simulated microgravity
have demonstrated the possibility of a significant
[72] and to characterise the effect of geomagnetic
overestimation of BRS when respiration was not
fluctuations on human body in space [68]. Ventilatory
controlled and/or was not of high frequency.
parameters have not been controlled/monitored in all
these studies. Microgravity results into an increase in
Whole body vibration respiratory, reduction in tidal volume and dead space.
Author could get only one abstract in MEDLINE End tidal PCO2 may also increase due to spacecraft
on the application of HRV analysis in whole body atmospheric conditions [73].
vibration. In this study [59], HRV, in conjunction with
subjective indices, has been used to characterise the Will Controlling Breathing Itself Influence HRV?
effect of different vibration frequencies on fatigue during
simulated driving. The study could display differential
Please also refer to section on ‘Tilt table studies &
effect of two frequencies (1.8 and 6 Hz) of whole body
LBNP’. There has been a concern that controlling
sinusoidal vibration in the vertical axis (0.05 G) on
breathing itself may change HRV due to cortical
sympatho-vagal balance discerned as LF/HF ratio.
involvement and confound the results. Patwardhan et al
Apparently, the respiratory parameters were not
[74] reported, in their first study, that controlled and
controlled/monitored. Such vibration is reported to cause
spontaneous breathing did not differ with regard to vagal
true hyperventilation due to alarm, stimulation of stretch
receptors in the lungs or superimposition of oscillatory control. He attributed the changes observed in his study
airflow on respiratory excursions [60]. It is likely that in HF power during metronomic breathing to ‘respiratory
variation in respiratory effects during exposure to the sinus arrhythmia versus breathing frequency
two different frequencies might have contributed to the relationship’ reported by Hirsch & Bishop [75] who have
observed difference in LF/HF ratio. reported that, for breathing frequencies greater than 0.1
Hz, respiratory sinus arrythmia amplitude (in beats/min)
decreased at the rate of approximately 20 dB/decade of
Psychophysiologic studies breathing frequency. Hirsch & Bishop [75] also showed
HRV indices have variously been used in that ‘respiratory sinus arrhythmia versus breathing
psychophysiological studies. In the field of aerospace frequency relationship’ was the same during both
medicine, the indices have been used with impunity for spontaneous and metronomic breathing. With the use
the assessment of human mental workload. These of this information, Patwardhan et al [74] calculated that
respiratory effects may induce changes in HRV indices for a 0.097-decade increase in breathing frequency (ie,
in an opposite direction. HRV indices are being tried also from the mean spontaneous breathing frequency of 0.24
as indicators of arousal [61] & fatigue [62] and for Hz to the metronomic breathing frequency of 0.30 Hz)
characterisation of personality [63]. In most of the respiratory arrhythmia should drop by 1.25 beats/min or
studies, none of the respiratory variables have been the oscillation in RR interval should decrease by about
controlled or monitored. Respiratory pattern is 21 ms. In their study, power in high frequency decreased
demonstrated to change with an increase in difficulty from 1932 to 733 ms2 ie, the oscillatory RR interval
[64]. Subjects breath slowly and deeply under mental amplitude decreased from 62 to 38 ms, a change (24 ms)
load [65]. consistent with that predicted using the results of Hirsch.

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Respiration And Heart Rate Variability : Lt Col KK Tripathi

However, in their second study, Patwardhan and monitoring respiratory variables is expressed and failure
his associates [76] reported that override of spontaneous to control / monitor breathing is accepted as one of the
respiratory pattern generator reduced HF power. limitations in the study [82].

Pagani et al [2] observed increase in heart rate and It is to be appreciated that the physiological origin
HF power during controlled respiration. This observation for these nonlinearities is unknown. From the
mathematical point of view, spectral measures resemble
is surprising in view of pacing frequency being higher
scaling indices when analyzed as normalized units during
than the mean breathing frequency of the subjects.
strictly controlled external conditions, because both
describe relative changes in the characteristics of HR
Results of Stark et al [77] further complicate the fluctuations over different time scales rather than the
issue. The authors examined no change in any of the magnitude of HRV. Certain studies have established the
spectral components of HRV while comparing correspondence between nonlinear and linear indices of
spontaneous breathing condition with a frequency HRV. For example, Francis et al [83] have shown that the
matched paced condition. This was despite a significant a1 and a 2 indices derived from, Detrended Fluctuation
Analysis, are simply frequency-weighted versions of the
increase in heart rate with an increase in breathing
spectral ratios LF/(HF + LF) and VLF/(LF + VLF),
frequency in both paced and unpaced conditions.
respectively. Similarly, Brennan et al [84] have shown
that SD1 & SD2 of Poincaré plot are related to time domain
Are Nonlinear HRV Measures Not Susceptibile To HRV measures as follows –
Respiratory Influences?
SD12 = ½Var (RRn - RRn+1) = ½SDSD2

Certain investigators [78] have reported that the

quantitative geometrical analysis of short-term RR SD22 = 2SDRR2 - ½SDSD2
interval variability from the Poincare plots (and also the
time domain measure RMSSD) were not significantly This further enacts exercise of caution in the
affected by changes in the breathing rate. Thus, these interpretation of nonlinear HRV estimates.
indices may be more suitable for the measurement of
cardiac vagal outflow during the ‘free-running’
Conclusions And Recommendations
ambulatory conditions wherein it is not possible to
measure/control the ventilatory parameters. Kanters et It should be clear from the foregoing review that a
multitude of respiratory influences can affect various
al [79] have shown that nonlinear dynamics in heart rate
HRV indices and may confound the results unless
variability is not a nonlinear input from the respiration
controlled. Even though interpretation of HRV indices
into the cardiovascular oscillator. The authors did not
derived from ‘free-running’ experiments with
find nonlinear dynamics (measured as the correlation spontaneous breathing could, sometimes, remain
dimension and the nonlinear prediction error) to differ unaffected in qualitative terms, it is always better and
significantly during spontaneous versus forced sometimes essential to control/factor out all such possible
respiration conditions. Occasionally, insusceptibility of confounders.
nonlinear HRV indices to breathing frequency and depth
has been quoted as a justification for not controlling or
References
monitoring the breathing [50].
1. Malik M. Heart rate variability-Standards of measurement,
physiological interpretation and clinical use. Task Force-
However, there are studies which have shown European Society of Cardiology and The North American
susceptibility of even nonlinear indices to ventilatory Society of Pacing and Electrophysiology. Eur Heart J 1996;
variables [80-81]. The requirement of controlling or 17: 354-81.

72 Ind J Aerospace Med 48(1), 2004

 Respiration And Heart Rate Variability : Lt Col KK Tripathi

2. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, 16. Abel FL and Waldhausen JA. Respiratory and cardiac effects
Pizzinelli P et al. Power spectral analysis of heart rate and on venous return. Am Heart J 1969; 78: 266-75.
arterial pressure variabilities as a marker of sympatho-vagal
17. Gilbey MP, Jordan D, Richter DW, Spyer KM. Synaptic
interaction in man and conscious dog. Circ Res 1986; 59:
mechanisms involved in the inspiratory modulation of vagal
178-93.
cardio-inhibitory neurons in the cat. J Physiol 1984; 365:
3. Pomeranz B, Macaulay RJ, Caudill MA, Kutz I, Adam D, 65–78.
Gordon D et al. Assessment of autonomic function in humans
18. Eckberg DL, Kifle YT, Roberts VL. Phase relationship
by heart rate spectral analysis. Am J Physiol Heart Circ
between normal human respiration and baroreflex
Physiol 1985; 248: H151-3.
responsiveness. J Physiol 1980; 304: 489–502.
4. Inoue K, Miyake S, Kumashiro M, Ogata H, Yoshimura O.
19. Eckberg DL. Physiological basis for human autonomic
Power spectral analysis of heart rate variability in traumatic
rhythms. Ann Med 2000. 32: 341-9.
quadriplegic. Am J Physiol Heart Circ Physiol 1990; 258:
H1722-6. 20. Daly de BM, Scott MJ. The effects of stimulation of the
carotid body chemoreceptors on heart rate in the dog. J
5. Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC,
Physiol 1958; 144: 148-66.
Cohen RJ. Power spectrum analysis of heart rate fluctuation:
a quantitative probe of beat-to-beat cardiovascular control. 21. Marshal JM. Peripheral chemoreceptors and cardiovascular
Science 1981; 213: 220-2. regulation. Physiol Rev 1994; 74: 543-94.
6. Ho KK, Moody GB, Peng CK, Mietus JE, Larson MG, Levy 22. Yasuma F, Hayano J. Augmentation of respiratory sinus
D et al. Predicting survival in heart failure case and control arrhythmia in response to progressive hypercapnia in
subjects by use of fully automated methods. Circulation 1997; conscious dogs. Am J Physiol Heart Circ Physiol 2001; 280:
96, 842-8. H2336-41.
7. Richman JS, Moorman JR. Physiological time-series analysis 23. Taylor EW, Jordan D, Coote JH. Central control of the
using approximate entropy and sample entropy. Am J Physiol cardiovascular and respiratory systems and their interactions
Heart Circ Physiol 2000; 278: H2039-49. in vertebrates. Physiol Rev 1999; 79: 855-916.
8. Brown TE, Beightol LA, Koh J et al. Important influence of 24. Hayano, J, Yasuma F, Okada A, Mukai S, Fujinami T.
respiration on human R-R interval power spectra is largely Respiratory sinus arrhythmia: a phenomenon improving
ignored. J Appl Physiol 1993; 75: 2310-17. pulmonary gas exchange and circulatory efficiency.
9. Schipke JD, Pelzer M, Arnold G. Effect of respiration rate Circulation 1996; 94: 842-47.
on short-term heart rate variability. J Clin Basic Cardiol 25. Dickstein J, Greenberg A, Kruger J, Robicsek A, Silverman
1999; 2: 92-4. JA, Sommer LZ et al. PCO2 affects tracheal tone during
10. Poyhonen M, Syvaoja S, Hartikainen J, Ruokonen E, Takala apnea in anesthetized dogs. J Appl Physiol 1996; 81:
J. The effect of carbon dioxide, respiratory rate and tidal 1184-9.
volume on human heart rate variability. Acta Anaesthesiol 26. Iscoe, S, and Fisher JT. Bronchomotor responses to hypoxia
Scand 2004; 48: 93-101. and hypercapnia in decerebrate cats. J Appl Physiol 1995;
11. Henry RA, Lu IL, Beightol LA, Eckberg DL. Interactions 78: 117-23.
between CO2 chemoreflexes and arterial baroreflexes. Am J 27. Sasano N, Vesely AE, Hayano J, Sasano H, Somogyi R,
Physiol Heart Circ Physiol 1998; 274: H2177-87. Preiss D et al. Direct effect of PaCO2 on respiratory sinus
12. Strauss-Blasche G, Moser M, Voica M, McLeod DR, arrhythmia in conscious humans. Am J Physiol Heart Circ
Klammer N, Marktl W. Relative timing of inspiration and Physiol 2002; 282: H973-6.
expiration affects respiratory sinus Arrhythmia. Clin Exp 28. Witte H, Zwiener U, Rother M, Glaser S. Evidence of a
Pharmacol Physiol 2000; 27: 601-6. previously undescribed form of respiratory sinus arrhythmia
13. Furutani Y, Shiigi T, Nakamura H, Nakamura Y, Ishizaki H, (RSA)- the physiological manifestation of ‘cardiac aliasing’.
Uchiyama K et al. Influence of the dead space induced by the Pflugers Arch 1988; 412: 442-4.
face mask on the measure of heart rate variability. J Cardiol 29. Novak V, Novak P, de Champlain J, Le Blanc AR, Martin
1997; 29: 171-6. R, Nadeau R. Influence of respiration on heart rate and
14. Hirsch JA, Bishop B. Human breathing patterns on blood pressure fluctuations. J Appl Physiol 1993; 74:
mouthpiece or face mask during air, CO2 or low O2. J Appl 617-26.
Physiol 1982; 53: 1281-90.
30. Badra LJ, Cooke WH, Hoag JB, Crossman AA, Kuusela TA,
15. Ludwig C. Beiträge zur Kenntniss des Einflusses der Tahvanainen KUO et al. Respiratory modulation of human
Respirationsbewegung auf den Blutlauf im Aortensystem. autonomic rhythms. Am J Physiol Heart Circ Physiol 2001;
Arch Anat Physiol 1847; 13: 242–302. 280: H2674-88.

Ind J Aerospace Med 48(1), 2004 73

Respiration And Heart Rate Variability : Lt Col KK Tripathi

31. Perini R, Milesi S, Biancardi L, Veicsteinas A. Effects of 46. Hong SK, Bennett PB, Shiraki K, Lin YC, Claybaugh JR
high altitude acclimatization on heart rate variability in (1996). Mixed-gas saturation diving. In: Fregly MJ, Blatteis
resting humans. Eur J Appl Physiol Occup Physiol 1996; CM, editors. Handbook of Physiology. Section-4:
73: 521-8. Environmental Physiology, Vol-II, Chapter-44, New York:
Oxford University Press, 1996: 1023-48.
32. Yamamoto Y, Hoshikawa Y, Miyashita M. Effects of acute
exposure to simulated altitude on heart rate variability during 47. Linnarsson D, Östlund A, Lind F, Hesser CM. Hyperbaric
exercise. J Appl Physiol 1996; 81: 1223-9. bradycardia and hypoventilation in exercising men: effects
of ambient pressure and breathing gas. J Appl Physiol 1999;
33. Liu XX, Lu LL, Zhong CF, Cheng ZH, Yuan Q, Ren HR. 87: 1428-32.
Analysis of heart rate variability during acute exposure to
hypoxia. Space Med Med Eng (Beijing) 2001. 14: 328-31. 48. Stepanov A, Stepanova S. Autonomic Nervous System in
the Patients with Coronary Artery Diseases during
34. Sevre K, Bendz B, Hanko E, Nakstad AR, Hauge A, Kasin JI. Hyperbaric Oxygenation Therapy. 1st Virtual congress in
Reduced autonomic activity during stepwise exposure to high Cardiology. Sep 1, 1999 to Ma 31, Mar 2000. Available
altitude. Acta Physiol Scand 2001; 173: 409-17. from URL: http://pcvc.sminter.com.ar/cvirtual/tlibres/
35. Melin A, Fauchier L, Dubuis E, Obert P, Bonnet P. Heart tnn2324/tnn2324.htm. Accessed on Jun 24, 2004.
rate variability in rats acclimatized to high altitude. High Alt 49. Lund V, Kentala E, Scheinin H, Klossner J, Sariola-Heinonen
Med Biol 2003; 4: 375-87. K, Jalonen J. Hyperbaric oxygen increases parasympathetic
36. Zhuang J, Zhu H, Zhou Z. Reserved higher vagal tone under activity in professional divers. Acta Anaesthesiol Scand 2000;
acute hypoxia in Tibetan adolescents with long-term 170: 39-44.
migration to sea level. Jpn J Physiol 2002. 52: 51-6. 50. Lund V, Laine J, Laitio T, Kentala E, Jalonen J, Scheinin H.
Instantaneous beat-to-beat variability reflects vagal tone
37. Smith CA, Dempsey JA, Hoenbein TF. Control of breathing
during hyperbaric hyperoxia. Undersea Hyperb Med 2003;
at high altitude. In: Hornbein TF, Schoene RB, editors. High
30: 29-36.
Altitude: An exploration of human adaptation. New York:
Marcel Dekker Inc, 2001: 139-73. 51. Yamazaki F, Wada F, Nagaya K et al. Autonomic mechanisms
of bradycardia during nitrox exposure at 3 Atmospheres
38. Milic-Emili J, Kayser B, Gautier H. Mechanics of breathing.
Absolute in humans. Aviat Space Environ Med 2003; 74:
In: Hornbein TF, Schoene RB, editors. High Altitude : An
643-8.
exploration of human adaptation. New York: Marcel Dekker
Inc, 2001: 175-98. 52. Lin YC, Hong SK (1996). Hyperbaria-breath hold dives. In:
Fregly MJ, Blatteis CM, editors. Handbook of Physiology.
39. Shida KK, Lin YC. Contribution of environmental factors
Section-4: Environmental Physiology, Vol-II, Chapt-42. New
in development of hyperbaric bradycardia. J Appl Physiol
York: Oxford University Press, 1996: 979-95.
1981; 50: 4731-5.
53. Mukai S and Hayano J. Heart rate and blood pressure
40. Neubauer B, Tetzlaff K, Staschen C, Bettinghausen E. Cardiac
variabilities during graded head-up tilt. J Appl Physiol 1995;
output changes during hyperbaric hyperoxia. Int Arch Occup
78: 212-6.
Environ Health 2001; 74: 119-22.
54. Jauregui-Renaud K, Marquez MF, Hermosillo AG, Sobrino A,
41. Yamauchi K, Tsutsui Y, Endo Y, Sagawa S, Yamazaki F, Shiraki Lara JL, Kostine A et al. Paced breathing can prevent
K. Sympathetic nervous and hemodynamic responses to lower vasovagal syncope during head-up tilt testing. Can J
body negative pressure in hyperbaria in men. Am J Physiol Cardiol 2003; 19: 698-700.
Regul Integr Comp Physiol 2002; 282: R38-45.
55. Patwardhan AR, Evans JM, Bruce EN, Knapp CF. Heart rate
42. Seals DR, Johnson DG, Fregosi RF. Hyperoxia lowers variability during sympatho-excitatory challenges:
sympathetic activity at rest but not during exercise in comparison between spontaneous and metronomic breathing.
humans. Am J Physiol Regul Integr Comp Physiol 1991; Integr Physiol Behav Sci 2001; 36: 109-20.
260: R873-8.
56. McKenzie I. Heart rate and blood pressure variability in
43. Davy KP, Jones PP, Seals DR. Influence of age on the subjects exposed to simulated increases in gravity. Exp
sympathetic neural adjustments to alterations in systemic Physiol 1993; 78: 825-34.
oxygen levels in humans. Am J Physiol Regulatory
Integrative Comp Physio 1997; 273: R690-5. 57. Pipraiya R. Study of the effects of +Gz acceleration on
autonomic control of heart rate and rhythm by the time
44. Lodato RF, Jubran A. Response time, autonomic mediation, domain and power spectral analysis. MD Thesis submitted
and reversibility of hyperoxic bradycardia in conscious dogs. to Rajiv Gandhi University of Health Sciences 2004. Institute
J Appl Physiol 1993: 74: 634-42. of Aerospace Medicine, Bangalore (INDIA).
45. Daly WJ, Bondurant S. Effects of oxygen breathing on the 58. Frederiks J, Swenne CA, TenVoorde BJ, Honzikova N, Levert
heart rate, blood pressure and cardiac index of normal men- JV, Maan AC et al. The importance of high-frequency
resting, with reactive hyperaemia and after atropine. J Clin paced breathing in spectral baroreflex sensitivity assessment.
Invest 1962; 41:126-32. J Hypertens 2000; 18: 1635-44.

74 Ind J Aerospace Med 48(1), 2004

 Respiration And Heart Rate Variability : Lt Col KK Tripathi

59. Jiao K, Li Z, Chen M, Wang C, Qi S. Effect of different 73. Prisk GK, Elliott AR, Guy HJ, Kosonen JM, West JB.
vibration frequencies on heart rate variability and driving Pulmonary gas exchange and its determinants during sustained
fatigue in healthy drivers. Int Arch Occup Environ Health microgravity on Spacelabs SLS-1 and SLS-2. J Appl Physiol
2004; 77: 205-12. 1995; 79: 1290-8.
60. Stott JRR. Vibration. In: Ernsting J, Nicholson AN, Rainford
74. Patwardhan AR, Evans JM, Bruce EN, Eckberg DL, Knapp
DJ, editors. Aviation Medicine. 3rd ed. Chapter-13, Oxford,
CF. Voluntary control of breathing does not alter vagal
UK Butterworth- Heinemann, 1999: 177-91.
modulation of heart rate. J App Physiol 1995; 78: 2087-94.
61. Galland BC, Reeves G, Taylor BJ, Bolton DPG. Sleep position,
autonomic function, and arousal. Arch Dis Child Fetal 75. Hirsch JA, Bishop B. Respiratory sinus arrhythmia in humans:
Neonatal Ed 1998; 78: F189–94. how breathing pattern modulates heart rate. Am J Physiol
Heart Circ Physiol 1981; 241: H620-9.
62. Egelund N. Spectral analysis of heart rate variability as an
indicator of driver fatigue. Ergonomics 1982; 25: 663-72. 76. Patwardhan AR, Vallurupalli S, Evans JM, Bruce EN, Knapp
63. Kamada T, Miyake S, Kamashiro M, Monou H, Inoue K. CF. Override of spontaneous respiratory pattern generator
Power spectral analysis of heart rate variability in Type As reduces cardiovascular parasympathetic influence. J App
and Type Bs during mental workload. Psychosom Med 1992; Physiol 1995; 79: 1048-54.
54: 462-70.
77. Stark R, Schienle A, Walter B, Vaitl D. Effects of paced
64. Wientjes CJE. Respiration in psychophysiology: Methods respiration on heart period and heart period variability.
and applications. Biol Psychol 1992; 34: 179-204. Psychophysiology 2000; 37: 302-9.
65. Veltman JA, Gaillard AWK. Physiological indices of workload 78. Penttila J, Helminen A, Jartti T, Kuusela T, Huikuri HV,
in a simulated flight task. Biol Psychol 1996; 42: 323-42. Tulppo MP et al. Time domain, geometrical and frequency
66. Miwa C, Sugiyama Y, Mano T, Iwase S, Matsukawa T. domain analysis of cardiac vagal outflow: effects of various
Sympatho-vagal responses in humans to thermoneutral head- respiratory patterns. Clin Physiol 2001; 21: 365-76.
out water immersion. Aviat Space Environ Med 1997; 68:
1109-14. 79. Kanters JK, Hojgaard MV, Agner E, Holstein-Rathlou NH.
Influence of forced respiration on nonlinear dynamics in
67. Baevsky RM, Moser M, Nikulina GA, Polyakov VV, Funtova heart rate variability. Am J Physiol Regulatory Integrative
II, Chernikova AG. Autonomic regulation of circulation and
Comp Physio 1997; 272: R1149-54.
cardiac contractility during a 14-month space flight. Acta
Astronaut 1998; 42: 159-73. 80. Fortrat JO, Yamamoto Y, Hughson RL. Respiratory
68. Baevsky RM, Petrov VM, Chernikova AG. Regulation of influences on non-linear dynamics of heart rate variability
autonomic nervous system in space and magnetic storms. in humans. Biol Cybern 1997; 77: 1-10.
Adv Space Res 1998; 22: 227-34.
81. Radhakrishna RK, Dutt DN, Yeragani VK. Nonlinear
69. Capderou A, Bailliart O, Maison-Blanche P, Kedra AW, Atkov measures of heart rate time series: influence of posture and
O, Techoueyres P. Parasympathetic activity during parabolic controlled breathing. Auton Neurosci 2000; 83: 148-58.
flight, effect of LBNP during microgravity. Aviat Space
Environ Med 2001; 72: 361-7. 82. Pikkujämsä SM, Mäkikallio TH, Sourander LB, Räihä IJ,
Puukka P, Skytta J et al. Cardiac interbeat interval dynamics
70. Beckers F, Seps B, Ramaekers D, Verheyden B, Aubert AE.
from childhood to senescence-comparison of conventional
Parasympathetic heart rate modulation during parabolic
and new measures based on fractals and chaos theory.
flights. Eur J Appl Physiol 2003; 90: 83-91.
Circulation 1999; 100: 393-9.
71. Migeotte PF, Prisk GK, Paiva M. Microgravity alters
respiratory sinus arrhythmia and short-term heart rate 83. Francis DP, Willson K, Georgiadou P, Wensel R, Davies LC.
variability in humans. Am J Physiol Heart Circ Physiol 2003; Physiological basis of fractal complexity properties of heart
284: H1995-2006. rate variability in man. J Physiol 2002; 542: 619–29.

72. Berlan M, Verhaeghe S, Pavy-Le Traon A, Thalamas C, 84. Brennan M, Palaniswami M, Kamen P. Do Existing Measures
Lafontan M, Marques MA. Yohimbine administration of Poincaré Plot Geometry Reflect Nonlinear Features of
prevents over-responsiveness to epinephrine induced by Heart Rate Variability? IEEE Trans Biomed Eng 2001; 48:
simulated microgravity. Aviat Space Environ Med 2000; 73: 1342-7.
735-42.

Ind J Aerospace Med 48(1), 2004 75