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Beat-To-Beat Blood Pressure and Heart Rate Responses To The Valsalva Maneuver

The document discusses the significance of measuring beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver as a test for autonomic function, emphasizing the advancements in non-invasive measurement techniques. It outlines the four phases of blood pressure responses during the maneuver and their implications for diagnosing conditions like sympathetic neurocirculatory failure. Additionally, it highlights the historical context of the Valsalva maneuver and its evolving understanding in relation to cardiovascular physiology.
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0% found this document useful (0 votes)
10 views16 pages

Beat-To-Beat Blood Pressure and Heart Rate Responses To The Valsalva Maneuver

The document discusses the significance of measuring beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver as a test for autonomic function, emphasizing the advancements in non-invasive measurement techniques. It outlines the four phases of blood pressure responses during the maneuver and their implications for diagnosing conditions like sympathetic neurocirculatory failure. Additionally, it highlights the historical context of the Valsalva maneuver and its evolving understanding in relation to cardiovascular physiology.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Author manuscript
Clin Auton Res. Author manuscript; available in PMC 2022 March 05.
Author Manuscript

Published in final edited form as:


Clin Auton Res. 2017 December ; 27(6): 361–367. doi:10.1007/s10286-017-0474-y.

Beat-to-Beat Blood Pressure and Heart Rate Responses to the


Valsalva Maneuver
David S. Goldstein, MD, PhD1, William P. Cheshire Jr, MD2
1Clinical
Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural
Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892 USA
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2Department of Neurology, Mayo Clinic, Jacksonville, FL 32224 USA

Abstract
Measurement of beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver is
the basis for a highly informative autonomic function test. Whereas in the past this measurement
required intra-arterial cannulation, the development of finger cuff devices that acquire arterial
pressure waveforms indistinguishable from those recorded intra-arterially has made it possible to
obtain accurate measurements noninvasively. In a patient with orthostatic hypotension, the pattern
of blood pressure responses during and after release of the maneuver can identify a neurogenic
basis—sympathetic neurocirculatory failure. The quantifiable change in cardiac interbeat interval
per unit change in systolic pressure during the maneuver can identify baroreflex-cardiovagal
failure.
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Keywords
Autonomic; Sympathetic; Parasympathetic; Valsalva; Blood Pressure

INTRODUCTION
Despite its apparent simplicity, the Valsalva maneuver is the basis for one of the most
important clinical physiological tests for autonomic failure. The test requires the use of a
method to measure blood pressure and heart rate continuously (beat-to-beat).

This is a limited review and does not cover areas such as confounding variables, technical
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aspects, and normative data. The goal here is mainly didactic.

Historical Perspective
In his De aure humana tractatus, published in Latin in 1704 (Figure 1), Antonio Valsalva
(1666–1723) described the maneuver that now bears his name. Valsalva devised the
maneuver not to track reflexive blood pressure responses to decreased cardiac filling but

Corresponding Author: David S. Goldstein, MD PhD, Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville
Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD 20892-1620 USA, Phone: 301-496-2103, Fax: 301-402-0180, iPhone:
301-675-1110, [email protected].
Goldstein and Cheshire Page 2

to clear material from the middle ear. According to one English translation given by Jellinek
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[18], Valsalva wrote, “… if with occluded mouth and nostrils air is compressed inwardly,
this action will extrude sanies from the middle ear [and is] a remedial exercise, to be
repeated, [and will lead to] extrusion of praeter-natural cerebral matter either via the wound,
via the nostrils, via the mouth, or via the auditory meatus … with great benefit …”

From this translation one might infer that the modern meaning of the Valsalva maneuver,
attempting to exhale against a resistance, is the opposite of the what Valsalva described.
Thus, the 1911 edition of the Encyclopedia Britannica contains the following entry: “By
a forcible expiration, the oral and nasal cavities being closed, air may be driven into the
tympanum, while a forcible inspiration (Valsalva’s experiment) will draw air from that
cavity. In the first case, the membrana tympani will bulge outwards, in the second case
inwards…” [21].
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On the other hand, Derbes and Kerr [6] translated the same passage as follows, “…if, I say,
he should attempt to compress the air within, after having closed the mouth and nostrils;
the exudate usually is pushed forth thereby copiously into the auditory meatus; so that I am
accustomed to recommend nothing more rapid in cleansing an ulcer of this kind, or remedy
more useful for the patient than a fairly frequent repetition of such an effort.” And an
editorial in the Journal of the American Medical Association used the following translation:
“Thus (in order to offer one of many proofs) if someone would instill a medicinal fluid into
the tympanic cavity or in the area of an ulcer or in the outer portion of the auditory meatus
and if now, with mouth and nose closed, an attempt is made to compress the air, fluid would
flow copiously from the auditory meatus. I recommend this for a prompt evacuation of a
suppurative lesion since this may be remedial for the illness which might not occur by itself”
[34].
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There is some controversy about priority with respect to the first description of the maneuver
that bears Valsalva’s name. Ambroise Pare (1510–1590) and Leonard of Bertipaglia (ca.
1380–1463) have also been mentioned.

Effects of the Valsalva maneuver on the cardiovascular system were not reported until
about 150 years later. In 1851, Ernst Heinrich Weber, a founder of the field of perceptual
psychology, demonstrated—in himself—a dramatic weakening of the pulse, loss of
consciousness, and convulsion after straining against a closed glottis and compression of
the chest [18]. A few years later Donders noted the typical increase in heart rate during
the maneuver [19]. There is a long history of interpreting the heart rate changes associated
with the maneuver in healthy individuals and patients with various cardiovascular disorders
[8]. This has been quantified by the heart rate ratio—the maximum heart rate during the
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maneuver divided by the lowest heart rate within 30 seconds of the peak heart rate.

In the early to mid-20th century Sharpey-Schafer reported systematic studies about effects of
the Valsalva maneuver on continuously recorded intra-arterial blood pressure in the normal
and failing heart [30]. In the 1960s Appenzeller described effects of cerebrovascular disease
on blood pressure responses to the maneuver [1] and findings in acute pandysautonomia [3]
and Parkinson’s disease [2].

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In the late 1980s non-invasive means to measure blood pressure for each pulse wave were
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introduced, enabling assessment of sympathetic neurocirculatory function by tracking the


beat-to-beat blood pressure responses to the Valsalva maneuver [17]. Finger cuff devices
such as the Finapres™ and NexFin™ photoplethysmography technologies measure blood
pressure indirectly via infrared light transmission. Light at this wavelength is primarily
absorbed by hemoglobin. Monitoring fluctuations in the intensity of the transmitted infrared
light through the finger provides information about the cross-sectional area that is occupied
by blood. The blood pressure is calculated from the dynamic changes in the volume of the
blood.

For non-invasive detection of sympathetic neurocirculatory failure by the characteristic


abnormalities in Phase II and Phase IV, the use of the finger cuff infrared and radial artery
tonometric methods was validated by comparison with simultaneously recorded intra-arterial
blood pressure [13]. Its validity and reliability having been established, the finger cuff
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method is now used widely to assess baroreflex-sympathoneural and baroreflex-cardiovagal


responses.

The Four Phases of the Blood Pressure Responses to the Valsalva Maneuver
When a person blows against a resistance for several seconds and then relaxes, the
continuously recorded blood pressure changes in a characteristic way. Four phases of this
change have been distinguished [14] (Figure 2).

In the first phase (Phase I), the moment the person begins to exhale against resistance,
intra-thoracic pressure increases suddenly, and the arterial blood pressure increases briefly.
One way to conceptualize the mechanism for the Phase I increase in pressure is that the
aortic blood is being forced out of the chest and down the arteries to the arms. This is a
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mechanical effect on intravascular distribution that has nothing to do with neural reflexes.

As the straining continues, the increased intrathoracic pressure impedes the return of venous
blood into the thorax. Reduced cardiac filling leads to a decrease in stroke volume, and
soon afterward systemic arterial pressure decreases (Phase II). These changes release
the sympathetic noradrenergic systemic from restraint by the low- and high-pressure
baroreceptors, and sympathetic outflows increase reflexively. Norepinephrine is released
from post-ganglionic sympathetic nerve terminals in the heart and blood vessel walls, the
norepinephrine binds to adrenoceptors, the arterioles constrict, total peripheral resistance to
blood flow increases, and near the end of Phase II the blood pressure increases from its
nadir, despite the fall in cardiac output.

One way to think of the reflexive changes in blood pressure during Phase II of the Valsalva
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maneuver is to consider the water pressure in a garden hose. If you were to turn down the
faucet, the pressure in the hose would decrease. You could bring the pressure back up by
tightening the nozzle.

In Phase III the person relaxes. Momentarily the blood pressure falls as intrathoracic
pressure returns to baseline. This is like a mirror image of the changes in Phase I—a
mechanical effect independent of reflexes.

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Finally, in Phase IV, since there is no longer an impediment to venous return to the heart,
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cardiac filling increases, and the heart ejects the blood into the reflexively constricted
vasculature. This is like your turning up the faucet of the garden hose, so that the rate of
filling of water into the hose is back to where it was originally—but the nozzle is still
tightened. The pressure overshoots. This is what happens normally to the blood pressure in
Phase IV of the Valsalva maneuver. The blood pressure increases rapidly and overshoots the
baseline pressure. Because of the overshoot and consequent arterial baroreflex stimulation,
sympathetic noradrenergic outflows are restrained, and the blood pressure soon decreases to
the baseline value.

Teleologically, if the brain “wanted” to maintain its blood flow in response to a fall in
arterial blood pressure, one way to do so would be to increase the heart rate. This is
what happens normally in Phase II. As the pressure falls below baseline, the heart rate
increases reflexively due to restraint of parasympathetic cardiovagal outflow. Thus, blockade
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of muscarinic cholinergic receptors by atropine markedly attenuates the increase in heart rate
during Phase II of the Valsalva maneuver, despite a larger decrease in blood pressure [12].

In most forms of autonomic failure, the abnormalities of blood pressure and heart rate
responses to the Valsalva maneuver occur together; however, there are exceptions. For
instance, in dopamine-β-hydroxylase deficiency, in which there is an inability to synthesize
norepinephrine, the blood pressure responses to the Valsalva maneuver are abnormal, but the
heart rate responses are normal [27]. Similar findings would be expected in an individual
with a high thoracic spinal cord transection [16].

Baroreflex-Cardiovagal Function
In 1969, Smyth, Sleight, and Pickering introduced what came to be called the “Oxford
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method” for quantifying baroreflex-cardiovagal sensitivity [33]. Blood pressure and cardiac
interbeat interval are tracked after bolus intravenous injection of a vasoconstrictor that does
not directly affect heart rate. Baroreflex sensitivity is defined as the slope of the relationship
between the interbeat interval (in milliseconds) vs. systolic blood pressure (in mmHg).
The scatterplot is based on the interbeat interval after a 1-beat delay, which approximates
the timing of the reflex. Originally, angiotensin was the vasoconstrictor, but because of
tachyphylaxis with repeated injections of angiotensin, this was changed to phenylephrine.
By this technique, Bristow et al. described decreased baroreflex sensitivity as a function of
high blood pressure [4].

In the early 1980s Goldstein compared 6 different techniques to assess baroreflex-


cardiovagal function, including the relationship between cardiac interbeat interval and
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systolic blood pressure during and after release of the Valsalva maneuver [11]. The average
intercorrelation among these measures (r = 0.36) was statistically significant but suggested
that variance in one measure accounted for an average of about 13% of the variance in
the others measures. Standard deviations across subjects were often as large as the mean,
indicating important inter-individual variability as well. These findings demonstrated that
baroreflex-cardiovagal sensitivity varies widely among subjects and that different techniques
for measuring baroreflex sensitivity probably measure different aspects of baroreflex
function.

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The Valsalva heart rate ratio is of limited value and is largely obsolete, because it does not
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take into account the dependence of the heart rate response on the blood pressure response.

Baroreflex-Sympathoneural Function
In a patient with baroreflex-sympathoneural failure—whether because of decreased ability
to modulate afferent traffic from arterial baroreceptors (e.g., from carotid arteriosclerosis
preventing pressure-related distortion of carotid sinus baroreceptors), dys-coordination of
input-output relationships among brainstem centers (Figure 3, e.g., from multiple system
atrophy), interference with ganglionic neurotransmission (e.g., from autoimmune autonomic
ganglionopathy), loss of sympathetic noradrenergic neurons (e.g., from pure autonomic
failure), lack of releasable stores of norepinephrine (e.g., dopamine-β-hydroxylase
deficiency), or decreased adrenoceptor-mediated responses (e.g., α-adrenoceptor blockade),
the same abnormal pattern of blood pressure occurs in Phase IV (Figure 2). Blood pressure
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increases slowly from the minimum value in Phase III, and there is no pressure overshoot.
This pattern of abnormalities can be more sensitive than measurement of orthostatic blood
pressure in detecting sympathetic neurocirculatory failure [28].

Conversely, if a patient had an abnormal blood pressure pattern in both Phase II (progressive
fall in pressure without recovery) and Phase IV (delayed return of pressure to baseline and
no overshoot), this would provide evidence for baroreflex-sympathoneural failure.

Compared to quantitative assessment of baroreflex-cardiovagal function by the decrease in


interbeat interval per unit decrease in systolic blood pressure during Phase II of the Valsalva
maneuver, which was introduced almost a half century ago [25], quantitative methods
to assess baroreflex-sympathoneural function by physiological responses to the Valsalva
maneuver are more recent. As noted above, baroreflex-sympathoneural failure manifests
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qualitatively by progressive fall in pressure during Phase II, slow return of blood pressure
toward baseline in Phase IV, and no pressure overshoot in Phase IV.

Investigators at the Mayo Clinic introduced a few techniques to accomplish this. Using
intravenous pharmacologic tools, Sandroni et al. distinguished separate physiologic
components of the sympathoneural response to the Valsalva maneuver. Whereas α-
adrenergic blockade with phentolamine blocked or markedly reduced the blood pressure
recovery during late Phase II and increased the blood pressure rise during Phase IV, β-
adrenergic blockade with propranolol attenuated the Phase IV blood pressure overshoot.
On this basis they concluded that the late Phase II response is dependent mostly
on peripheral α-adrenergic innervation and Phase IV is dependent mostly on cardiac
β-adrenergic innervation [28]. Schrezenmeier et al. validated an index of “adrenergic
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baroreflex sensitivity” based on the pressure recovery time in Phase IV and the preceding
decrease in pressure during Phase II [29]. The most sensitive method is to measure the
pressure recovery time (PRT), defined as the time for the blood pressure to return to baseline
during Phase IV [36]. Because the extent of variability of the PRT depends on the value
for PRT, the log of the PRT may be more appropriate for comparisons with normal. Novak
preferred the difference in blood pressure between baseline and the end of Phase II [23].
Rahman et al. applied the trapezoid method to calculate “baroreflex areas” corresponding to

Clin Auton Res. Author manuscript; available in PMC 2022 March 05.
Goldstein and Cheshire Page 6

the areas under the curve from baseline pressure in Phases II and IV (Figure 2 [25]. For a
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single overall measure they proposed the log of the sum of the two areas [26].

Although quantitative measures of baroreflex-sympathoneural function have been published,


for clinical purposes a qualitative description of the blood pressure trends at the end of Phase
II and in Phase III-IV seems sufficient, along with noting the PRT.

The “Square Wave” Response


In some people, instead of blood pressure decreasing to below baseline during Phase II
of the Valsalva maneuver, the pressure fails to decrease or can even increase. The Phase
III fall in pressure is still present, but because blood pressure did not drop during Phase
II – the stimulus for activation of sympathetic noradrenergic outflow – there is no Phase
IV overshoot in pressure. This has been called the “square wave response” or the “flat top
response” because of the pattern of the pressure during and after the maneuver resembling a
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mathematical square wave sign [35].

The square wave response occurs in situations where there is increased cardiac filling
coupled with increased sympathetic noradrenergic outflow. The most well-known example
is congestive heart failure [30]. In healthy people, infusion of norepinephrine increases
cardiac filling and changes the shape of the blood pressure pattern to the square wave
phenomenon [24]. We noted this in a healthy subject who performed the Valsalva maneuver
and had intra-arterial blood pressure recorded continuously, under resting conditions and
after rapid infusion of 2 liters of ice-cold saline via a centralized IV catheter to induce mild
core hypothermia [9]. The infusion, which increased central venous pressure, resulted in
profound, generalized sympathetic noradrenergic activation [10]. As shown in Figure 4, the
infusion of cold saline produced the square wave phenomenon.
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Parameters of the Valsalva Maneuver in Autonomic Function Testing


Different centers use different methods of measuring beat-to-beat hemodynamic responses
to the Valsalva maneuver as part of autonomic function testing. The duration varies from 10–
20 seconds, and the intensity varies from 30–40 mmHg; or else the subject strains against a
closed glottis. The subject usually is supine with head on pillow, although arterial baroreflex
gain is not particularly affected by upright posture [7]. If a square wave response is noted,
the subject may be tilted head-up to 20 degrees from horizontal to decrease cardiac filling,
resulting in a greater fall in blood pressure during Phase II at the expense of decreased
specificity of the test due to postural activation of sympathetic outflow [19, 35].

Concurrent Measurements
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In order to verify that the subject has delivered the target positive pressure for the targeted
duration, it is highly advisable to record the delivered pressure.

Performance of the Valsalva maneuver is associated with a transient wave of sweating,


which can be detected by tracking skin electrical conductance. This can be worthwhile,
because the absence of sweating during the Valsalva may indicate deficiency of the
sympathetic cholinergic system. In other words, tracking beat-to-beat blood pressure, heart

Clin Auton Res. Author manuscript; available in PMC 2022 March 05.
Goldstein and Cheshire Page 7

rate, and skin electrical conductance can provide information about the status of three
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components of the autonomic nervous system simultaneously—sympathetic noradrenergic,


parasympathetic cholinergic, and sympathetic cholinergic. There have been no studies on the
validity and clinical utility of measuring skin electrical conductance during the performance
of the Valsalva maneuver; however, this is a well accepted measure of dynamic changes in
sweat production, which is an autonomically-mediated response.

Relatively recent advances include recording of skeletal muscle sympathetic nerve activity
by peroneal microneurography [5] and functional magnetic resonance imaging during the
Valsalva maneuver [15]. These are two of several research findings that require technologies
not available at most autonomic testing centers.

Effects of Aging or Bed Rest


Many cross-sectional studies have shown that baroreflex-cardiovagal gain decreases as a
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function of subject age. The smaller literature about aging effects on baroreflex-cardiovagal
gain as assessed by interbeat interval and systolic blood pressure responses to the Valsalva
maneuver fit with this inference. Most of this literature refers to data from Phase IV
[22]. Based on Phase II data, baroreflex-cardiovagal gain has been reported to be weakly
negatively correlated with subject age [11], but at least one report found no aging-related
decline in baroreflex-cardiovagal gain based on Phase II data [20]. There are no longitudinal
studies on this topic.

In using the magnitude of fall in systolic blood pressure during Phase II and the Phase IV
overshoot to gauge sympathetic neurocirculatory function, one should bear in mind that the
former is related positively and the latter negatively to normal aging [31]. This means that
compared groups in clinical research reports should be of similar age.
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Prolonged bed rest has been reported to augment the fall in pressure in Phase II and to
increase the Phase IV pressure overshoot [32].

A Closing Anecdote
The paternal grandfather of the second author of this paper, having ruptured both tympanic
membranes in 1918 during a grenade explosion in the trenches in World War I, from his
hospital bed wrote about his personal experience with the Valsalva maneuver:

I just discovered last night that I can breathe through my ears! And I can shut my
mouth, take a long breath, hold my nose, lean back my head, and blow out the two
candles on each side of the head of my bed with my ears! It is the best parlour stunt
going, and when I get home, the only work I am going to do is to hire myself out to
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blow out the candles on birthday cakes at parties, and I feel sure I shall get rich at
it.
(Text of a letter from James Webb Cheshire (1890–1980) to Mrs. Joseph Blount
Cheshire, from Base Hospital No. 18, American Expeditionary Force, France,
March 3, 1918)

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Goldstein and Cheshire Page 8

Forcibly exhaling did not seem to have caused symptomatic hypotension in his case, despite
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prolonged bed rest [32], because he refused the order to be discharged home and, though
injured, returned to combat on the Hindenburg line.

Figure 5 shows still images from a YouTube video of a person blowing up a balloon through
his ear. The video can be accessed at https://www.youtube.com/watch?v=qf1VA22s92E.

Financial support:
The research reported here was supported by the Division of Intramural Research, NINDS, NIH.

Abbreviations:
AAG autoimmune autonomic ganglionopathy
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ANS autonomic nervous system

COI chronic orthostatic intolerance

NE norepinephrine

MSA multiple system atrophy

OH orthostatic hypotension

OI orthostatic intolerance

PAF pure autonomic failure

PNS parasympathetic nervous system


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POTS postural tachycardia syndrome

SAS sympathetic adrenergic system

SCS sympathetic cholinergic system

SEC skin electrical conductance

SNS sympathetic noradrenergic system

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SYNOPSIS
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Beat-to-beat Blood Pressure and Heart Rate Responses to the Valsalva Maneuver
Measuring beat-to-beat blood pressure and heart rate responses to the Valsalva
maneuver is a valuable autonomic function test, which can establish whether orthostatic
hypotension is neurogenic and can be used to assess baroreflex-cardiovagal function.
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Figure 1:
Text from Valsalva’s De aure humana tractatus.
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Figure 2: Four Phases of the heart rate and blood pressure responses to the Valsalva maneuver.
Areas in aqua illustrate increased areas under the baseline blood pressure in Phase II and
Phase IV in neurogenic orthostatic hypotension.
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Figure 3: Diagram of brainstem pathways mediating baroreflxes.


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Abbreviations: BP=blood pressure; CVLM=caudal ventrolateral medulla; Dec.=decreased;


hi-P=high pressure; HR=heart rate; lo-P=low pressure; NTS=nucleus of the solitary tract;
NA=nucleus ambiguus; SNS=sympathetic noradrenergic system; X=vagus (the tenth cranial
nerve). The baroreflex arcs involve negative feedback loops, indicated by an odd number of
(−) signs across the stations in the loop.
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Figure 4: The square wave response evoked by central IV infusion of cold saline.
The top panel shows intra-arterial pressure associated with the Valsalva maneuver at
baseline, and the bottom panel shows the pressure associated with the Valsalva maneuver in
the same subject near the end of a 2-liter infusion of ice-cold saline over about 20 minutes
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via a centralized large-bore catheter. Note that at baseline, during the maneuver blood
pressure decreases below baseline, whereas with cold saline infusion the blood pressure
failes to decrease below baseline—the square wave response (flat-top response).
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Figure 5: Still images from a YouTube video clip of a man blowing up a balloon through his ear.
The video can be accessed at https://www.youtube.com/watch?v=qf1VA22s92E. Permission
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to reproduce these images was obtained from Diagonal View (www.diagonal-view.com).


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Clin Auton Res. Author manuscript; available in PMC 2022 March 05.

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