JEPonline
Journal
of
Exercise
Physiologyonline
ISSN
1097-9751
An
International Electronic
Journal
for Exercise Physiologists
Vol 1 No 3 October 1998
|
Systems
Physiology: Cardiopulmonary
Heart
rate variability and baroreceptor responsiveness to evaluate autonomic
cardiovascular adaptations to exercise
WILLIAM H. COOKE
Department of Internal
Medicine, Division of Cardiology, Medical College of Virginia at Virginia
Commonwealth University, Richmond, Virginia
WILLIAM H. COOKE. Heart
rate variability and baroreceptor responsiveness to evaluate autonomic
cardiovascular adaptations to exercise. JEPonline
Vol.
1 No. 3 1998. Exercise physiologists routinely
evaluate adaptations to exercise such as aerobic capacity, muscular strength
and flexibility, and body composition, but often overlook the effects of
exercise training on autonomic regulation of cardiovascular function. A
preponderance of cross-sectional studies report significant resting sinus
bradycardia and high heart rate variability in active subjects, and suggest
that exercise training induces adaptations in autonomic cardiovascular
control. Alternatively, data from cross-sectional studies leave open the
possibility that individuals with a genetic predisposition for lower heart
rates or greater heart rate variability are also endowed with greater aerobic
capacity. Conflicting results from a limited number of exercise training
studies fail to conclusively demonstrate a direct effect of exercise training
on the autonomic nervous system. In this report I suggest that simple measures
of heart rate variability during controlled frequency breathing, and arterial
baroreceptor responsiveness to Valsalva's maneuver provide unique insights
into autonomic regulation of cardiovascular function. I propose that systemic-wide
integration of exercise training effects might be better characterized
if exercise physiologists would perform tests of autonomic function in
conjunction with standard exercise tests during routine laboratory evaluations.
Key Words: CARDIAC
CONTROL, CONTROLLED BREATHING, VALSALVA MANEUVER
Introduction
Chronic aerobic exercise elicits important
cardio-protective adaptations that have been linked to decreased all-cause
mortality (1). Effects such as increased aerobic capacity
(consequent to decreased peripheral vascular resistance and increased cardiac
output and arteriovenous oxygen difference) are well documented (2,3),
and characterize the physiological adaptation to endurance training. Surprisingly,
despite important implications for cardiovascular health, the effects of
aerobic exercise on autonomic cardiovascular regulation (4,5)
receive comparatively less attention. Effects such as significant resting
sinus bradycardia and increased heart rate variability [the latter being
inversely related to mortality after myocardial infarction (6)],
are thought to be mediated through adaptations in autonomic cardiovascular
control (7).
Analyses of heart rate variability and
baroreceptor responsiveness provide important information on exercise training
effects. High heart rate variability is associated with increased parasympathetic
cardiac control, and low heart rate variability is associated with decreased
parasympathetic cardiac control and coronary heart disease (8).
Heart rate variability was shown to be significantly higher in physically
active, compared to non-physically active healthy humans (4,7).
Conversely, decreased vagal outflow after myocardial infarction results
in both decreased heart rate variability and baroreceptor responsiveness
(9,10).
Although not consistently found (11), some have reported
increased arterial baroreceptor sensitivity in active, compared to sedentary
humans (12,13). Taken together, these
data suggest that the autonomic nervous system adapts to chronic demands
imposed by exercise or inactivity.
Many applied exercise physiology laboratories
evaluate the effects of exercise on functional rather than autonomic adaptations
despite being equipped to do both. Autonomic function tests, performed
in conjunction with standard exercise tests, would more completely inform
mechanisms of systemic-wide adaptations to exercise, and contribute importantly
to the evaluation of physical fitness and cardiovascular health. In this
report, I provide rationale for the exercise physiologist to consider tests
of heart rate variability and baroreceptor responsiveness, and briefly
describe simple procedures that may easily be performed as an adjunct to
standard exercise tests during routine evaluations.
Heart Rate Variability
During supine rest, inspiration causes
an increase, and expiration a decrease in heart rate. These spontaneous
fluctuations in sinus node rate, known collectively as heart rate variability,
are under dual neural control from both parasympathetic and sympathetic
sources (14). At normal respiratory frequencies and
tidal volumes, variations in beat-to-beat heart period (R-R interval) are
proportional to, and predominantly controlled by parasympathetic activity.
Thus, analysis of R-R interval oscillations at or around the respiratory
frequency directly reflects parasympathetic cardiac control (15).
Time Domain Analysis: Time
domain analytical methods are easy to apply to fluctuations in heart rate.
Simple analysis of heart rate or R-R interval, or the difference between
the longest and shortest R-R interval may be calculated from continuous
QRS complexes. A recent Task Force report (16) summarized
various time-domain methods lending insights into analysis of short- and
long-term heat rate variability. One of the most widely used methods involves
calculating the standard deviation from the mean R-R intervals of all cardiac
cycles occurring during a given time period (usually ~ 5 min). Assuming
normal respiratory frequencies, a simple standard deviation of R-R intervals
calculated before and after an exercise program would provide the exercise
physiologist with general information about the effects of the program
on parasympathetic cardiovascular control. Although quantitative values
for heart rate variability vary widely between groups of matched subjects
[highlighting the need to standardize autonomic function tests], Figure
1 presents a generalized continuum of values for R-R interval standard
deviations among groups of diseased, healthy, and active subjects. Time
domain analytical methods are valuable, but for a more complete understanding
of mechanisms underlying autonomic regulation of cardiovascular function,
frequency domain analyses may be employed.
Frequency Domain Analysis: Akselrod
et al. (17) demonstrated the usefulness of applying
power spectral analysis (the distribution of variance as a function of
frequency) to beat-by-beat fluctuations in heart rate. Fast Fourier transform-based
spectral analyses are commonly used, and widely available as a component
of many data analysis software packages. It should be mentioned that significant
data transformation is required before data may be submitted to power spectral
analysis. Briefly, to calculate R-R interval spectral power, it is recommended
that the continuous electrocardiogram be initially sampled at rates between
250 to 500 Hz. The digitized signal must be checked for artifacts, and
any such artifacts (such as extrasystoles, movement, muscular contraction)
should be removed and replaced with markers calculated from preceding R-R
interval means. Data must be equidistant, therefore resampling of the data
(either via linear or polynomial interpolation) is required. There are
a number of power spectral analyses that may be employed. Excellent reviews
on this topic are available (16,18,19).
As an example, in our laboratory we recently calculated R-R interval power
spectra as follows: The non-equidistant R-R interval time series was spline
interpolated (cubic), resampled at 4 Hz, and passed through a finite low-pass
impulse response filter with a cut-off frequency of 0.5 Hz. Data sets comprising
64 s (256 samples), sliding every 10 s, were trend eliminated (linear regression),
windowed (Hanning method), and fast Fourier transformed. We used the periodogram
method to estimate power distribution. Power was expressed as the area
under the spectrum over the frequency range of interest
(20). In short term recordings, one typically sees three peaks of spectral
power: very low frequency (less than ~ .04 Hz), low frequency (.04 to .15
Hz), and high frequency (.15 to .4 Hz) (16). The physiological
significance of very low frequency oscillations is unclear; these oscillations
are not usually considered when analyzing the periodicity of short term
cardiovascular fluctuations. Fluctuations within the low- and high-frequency
ranges, however, provide insight into autonomic efferent neural outflow.
Parasympathetic and sympathetic neural
discharges are modulated by central and peripheral regulatory mechanisms
which constantly interact to 'fine tune' beat-to-beat cardiac control.
Interactions between parasympathetic and sympathetic outflow result in
relatively short- and long-term heart rate fluctuations that are interpretable
with power spectral analysis. High frequency oscillations are mediated
by parasympathetic, whereas low frequency oscillations are mediated by
both parasympathetic and sympathetic contributions (17).
For the exercise physiologist, increased high frequency spectral power
after training is indicative of increased parasympathetic cardiac control.
Liao et al. (21) recently showed that heart rate variability
is significantly different among groups differing in age, race, and sex.
Group-matching of subjects should be considered.
Controlled Frequency Breathing:A
recent study by our laboratory showed that various controlled breathing
protocols yield similar information regarding cardiovascular rhythms
(20). However, it is incorrect to suggest that respiratory input is
unimportant to the assessment of heart rate variability. Variability in
tidal volume and respiratory frequency is high when subjects breathe spontaneously
(without respiratory frequency control) (22); when breathing
is variable, the interpretation of autonomic cardiac control may be confounded.
Brown et al. (22) showed that R-R interval spectral
power is influenced profoundly by respiratory input, and concluded that
respiration must be taken into account to properly assess heart rate variability.
When the breathing rate is controlled at frequencies lower than normal
respiratory frequencies (below ~ 12 breaths/min), low frequency and high
frequency R-R interval oscillations tend to merge (20),
making it impossible to evaluate parasympathetic neural outflow without
pharmacological blockade. For these reasons, the effects of an exercise
training program on parasympathetic cardiac control should be evaluated
using strict control of respiratory rate [at or around normal respiratory
frequencies (~ 12 to 15 breaths/min)]. Respiratory and R-R interval spectral
power derived from uncontrolled and controlled breathing protocols are
displayed for comparison in
Figure 2 .
Suggested Methods and Procedures:
At the minimum, to perform a controlled breathing protocol it is necessary
to record beat-to-beat ECG. Respiratory rate must be strictly controlled.
The subject should be allowed a period of supine rest followed by a period
of controlled frequency breathing for at least 5 minutes. Respiratory rate
should be constant, and set between 12 and 15 breaths per minute (0.2 -
0.25 Hz) using a metronome, pre-recorded audio tape, or in-house computer
software.
Baroreceptor Responsiveness
Arterial baroreceptors are arterial pressure
sensors, located on the walls of the carotid sinuses and aortic arch. Baroreceptors
send afferent signals to the cardiovascular control center to modulate
autonomic activity as a function of arterial pressure. Through the integrated
activities of the baroreceptors and autonomic efferent outflow, the inverse
relationship between arterial pressure and heart rate is regulated on a
second-by-second basis. Although there are a number of techniques available
to assess baroreflex function, not all are possible within the realm of
the common applied exercise physiology laboratory. One technique that is
possible, and highly informative, is Valsalva's maneuver.
Valsalva's Maneuver: The
act of exhaling forcefully against a closed glottis, or 'Valsalva's maneuver'
[named for Antonio Maria Valsalva (1666-1723)], evokes hemodynamic responses
by way of immediate increases in intra-abdominal and intra-thoracic pressures.
Consequent to straining, venous return to the heart is impeded, resulting
in predictable increases and decreases in arterial pressure and autonomic
neural activity. Either heart rate alone, or reciprocal relations between
arterial pressure and heart rate are used to assess baroreceptor sensitivity
(23).
Valsalva standardization procedures have
not been documented, and tests may vary according to the depth of inspiration
before straining, the straining pressure at the mouth, the duration of
straining, and the position of the subject during straining. All of these
variables could potentially influence arterial pressure responses to varying
degrees. However, in spite of different testing protocols, the response
to Valsalva's maneuver in normal subjects can generally be described in
four phases: 1) an increase in arterial pressure and decrease in heart
rate upon straining; 2) a fall, then recovery of arterial pressure accompanied
by an increase in heart rate; 3) a brief reduction of arterial pressure
and increase in heart rate at the release of straining; and 4) a sustained
elevation of arterial pressure and slowing of heart rate [see Eckberg and
Sleight (23) for a thorough description]. Patients with
certain forms of heart disease exhibit 'square wave' responses characterized
by a lack of decrease in arterial pressure during straining, and subsequent
lack of sympathetic activation (24). Representative
arterial pressure responses to Valsalva's maneuver in one healthy subject
are shown with R-R interval, muscle sympathetic nerve activity (peroneal
nerve microneurography), and respiration in Figure
3.
In Figure
3 it is interesting to observe reciprocal relations between arterial
pressure and muscle sympathetic nerve activity. The dramatic increase in
arterial pressure apparent during phase four is accompanied by inhibition
of sympathetic activity and dramatic slowing of the heart rate (increased
R-R interval).
Because the use of arterial catheters is
highly invasive, beat-to-beat measures of arterial pressure are not always
possible unless the laboratory is equipped with a finger photoplethysmograph
device (such as a Finapres, Ohmeda, Englewood, CO). Assuming that no such
device is available, baroreceptor responsiveness may still be evaluated
from changes in heart rate. Levin
(24) described the
Valsalva ratio, which was simply the ratio of the maximal to the minimal
R-R interval measured during the maneuver. The reproducibility of this
analysis was good; average differences were about 5% when a second trial
was performed one week after the first. Average Valsalva ratios for normal,
healthy subjects ranged from 1.3 to 2.9, with greater than 50% of the 30
subjects studied showing values above 1.9 (24). The
Valsalva ratio could easily be obtained during a fitness evaluation and
compared to values recorded after a period of exercise training. Admittedly,
the Valsalva ratio is largely a 'rough estimate' of baroreflex responsiveness.
Greater sensitivity and accuracy is achieved if the laboratory is equipped
to measure beat-by-beat arterial pressure.
Excellent insight into baroreceptor responsiveness
may be obtained by analyzing heart rate and arterial pressure responses
to phase four of Valsalva's maneuver. In this analysis, the slope of the
linear regression between systolic pressure and R-R interval is calculated,
and baroreflex sensitivity is defined as changes in R-R interval as a function
of changes in systolic pressure. Kautzner et al. (25)
described this procedure in detail, and also calculated baroreflex sensitivity
as the simple ratio of maximal and minimal R-R interval to maximal and
minimal systolic pressure; baroreflex sensitivity was not significantly
different when calculated by the linear regression (13.7 ± 8.4 ms/mmHg)
vs. the ratio (15.3 ± 8.8 ms/mmHg) method. Either procedure would
be appropriate to assess baroreflex sensitivity in the exercise physiology
laboratory.
Suggested Methods and Procedures:At
the minimum, the subject should be instrumented for ECG, fitted with a
noseclip, and then to a mouthpiece device connected via a short plastic
tube to a mercury manometer or Statham pressure transducer. Mercury manometers
provide direct visual feedback so the subject may maintain the required
expiratory pressure. Visual feedback from a calibrated Statham pressure
transducer can be achieved by routing the analog output signal through
an oscilloscope (and then to a digital converter). To insure that expiratory
pressure is not simply maintained by closing the glottis, a small leak
should be incorporated into the system. If available, beat-to-beat arterial
pressure should be measured. Responses to Valsalva's maneuver are directly
proportional to expiratory effort, and 30 mmHg for 15 seconds in the supine
position seems to produce maximal responses (25,26).
To perform a Valsalva, subjects should breathe at a controlled rate (12
to 15 breaths/min) for at least 30 seconds followed by a 15-second strain
initiated at the same time in the breathing cycle (i.e. at the end of a
normal inspiration). Recovery durations should be long enough for arterial
pressure and heart rate to stabilize (~ 2 min), during which time the subject
should maintain the control of breathing.
Summary
In this brief report, I suggest that thorough
evaluations of exercise training responses should include basic tests of
autonomic regulation. Autonomic function tests explore cardio-protective
adaptations such as increased parasympathetic cardiac control, are useful
in identifying pathophysiological conditions (square wave Valsalva response),
and add importantly to our understanding of systemic-wide integration of
exercise training effects. Simple measures of heart rate variability during
controlled frequency breathing, and arterial baroreceptor responsiveness
to Valsalva's maneuver could easily be incorporated into standard exercise
evaluations as a means to quantify autonomic adaptability.
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Please note new address for correspondence:
William H. Cooke, PhD, Assistant Professor
of Applied Physiology, Michigan Technological University, Center for Biomedical
Engineering,1400 Townsend Drive, Chem. Sci. 312, Houghton, Michigan 49931
Copyright ©1998
American
Society of Exercise Physiologists
All Rights Reserved
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