From the Autonomic Disorders Center, Department of Neurology, Mayo Clinic
and Foundation, Rochester, Minn.
Correspondence to Phillip A. Low, MD, Autonomic Disorders Center, Department of Neurology, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. E-mail low.phillip{at}mayo.edu
Methods—We studied 21 patients (aged 52 to 78 years) with
neurogenic OH during 80° head-up tilt. Blood flow velocities (BFV)
from the middle cerebral artery were continuously monitored with
transcranial Doppler sonography, as were heart rate,
blood pressure (BP), cardiac output, stroke volume, CO2,
total peripheral resistance, and cerebrovascular
resistance.
Results—All OH patients had lower BP (P<.0001),
BFV_diastolic (P<.05), CVR
(P<.007), and TPR (P<.02) during
head-up tilt than control subjects. In control subjects, no
correlations between BFV and BP were found during head-up tilt,
suggesting normal autoregulation. OH patients could be separated into
those with normal or expanded autoregulation (OH_NA; n=16) and those
with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either
no correlation between BFV and BP (n=8) or had a positive BFV/BP
correlation (R2>.75) but with a flat slope.
An expansion of the "autoregulated" range was seen in some
patients. The OH_AF group was characterized by a profound fall in BFV
in response to a small reduction in BP (mean
Conclusions—The most common patterns of cerebral response to OH
are autoregulatory failure with a flat flow-pressure relationship or
intact autoregulation with an expanded autoregulated range. The least
common pattern is autoregulatory failure with a steep flow-pressure
relationship. Patients with patterns 1 and 2 have an enhanced capacity
to cope with OH, while those with pattern 3 have reduced capacity.
Cerebral perfusion cannot be predicted from the BP alone, since the
relationship between BP and cerebral perfusion is nonlinear because of
autoregulation. The primary goal of cerebral autoregulation is to
maintain constant blood flow during variations in BP.3
Within the autoregulated range (
Fourteen healthy control subjects (6 men and 8 women; mean age,
61.6±2.3 years [range, 29 to 77 years]) were also studied. Age was
not significantly different between the groups. Normal control subjects
were selected as follows. Mayo Clinic histories were reviewed, and all
subjects also completed a questionnaire directed at ruling out
peripheral neuropathy and autonomic disorders.
They were free of alcoholism, diabetes, malnutrition, obesity, and
illnesses or medications known to affect the autonomic nervous system.
No food, coffee, or nicotine was permitted for 3 hours before the
study.
Protocol
Hyperventilation
Data Acquisition, Processing, and Analysis
Transcranial Doppler
The TCD system (Multigon Industries) was used to continuously
monitor cerebral BFV during the tilt-table test and during
hyperventilation. The left MCA was insonated from the anterior temporal
window by placing the probe on the temporal area, above the zygomatic
arch. The polytetrafluoroethylene probe was
positioned to record the maximal MCA velocity and fixed at the
desired angle with the
polytetrafluoroethylene probe holder, which
allowed three-dimensional manipulation of the probe angle. Stable
positioning of the probe is crucial for continuous data
recording and for data evaluation. Doppler shift, a
difference between the frequency of the emitted signal (2 MHz) and its
echo (frequency of the reflected signal), was then used to calculate
the velocity of blood flow by means of Fourier transform. Spectral
analysis of blood flow velocities is then presented as
a waveform, similar to the BP waveform. Analog flow velocity waveforms
were continuously recorded and used for off-line detection of
systolic (BFV_S) and diastolic blood flow
velocities (BFV_D) on a beat-to-beat basis. Mean blood flow velocity
(BFV_M) was computed according the formula described above (see derived
and calculated variables in "Selected Abbreviations and
Acronyms"). Several assumptions must be made to evaluate cerebral
autoregulation with TCD monitoring. An assumption that the diameter of
the MCA does not change must be made to relate MCA flow velocity to
blood flow. Flow velocity can be increased because of an increased flow
through the arterioles distal to the probe or by a constriction of the
insonated trunk. The caliber of the MCA stem (the insonated segment in
TCD) is reported to change by <4% in response to BP and
CO2 changes.8 Larger changes in trunk caliber
can occur, but only under extreme circumstances such as
subarachnoid hemorrhage or injury to the vessel. The
changes in BFV_M, pulsatility index, and resistance index therefore
reliably reflect, under nonextreme circumstances, changes in the tone
of arterioles and, perhaps, small arteries.8 Additionally,
cerebral BFV correlates well with cerebral blood flow measured with
xenon clearance9 or with laser Doppler
flux.10 We expressed CVR as mm Hg/cm per second. It
can alternatively be expressed in units of dyne.s/cm-3 by
multiplying by 1333.
Impedance Cardiography
Changes in thoracic impedance during the cardiac cycle largely
reflect changes in thoracic aortic volume and hence in left
ventricular outflow.11 Impedance cardiography
(NCCOM3-R7 Cardiodynamic Monitor, BoMed Medical Manufacturing) used
eight electrodes placed on the thoracic outlet and inlet. All subjects
had normal cardiovascular function and were free of
intraventricular conduction defects, intracardiac
shunts, or valvular insufficiency that may confound SV and CO
measurement. Values of SV and CO were calculated with the use of
Kubicek's equation.12 This equation uses adjustments for
the body surface area that may account for interindividual variation of
the impedance estimate.
Respiration and CO2
Respiratory frequency was measured with a nasal thermistor and
sampled at 4 Hz. CO2 was measured from the expiratory flow
with a Puritan Bennet 254 airway gas monitor calibrated with 5%
CO2. All data were simultaneously acquired;
outlying values and extrasystoles were removed. Time series were then
averaged over 30-second intervals for each parameter for
each individual. These individual temporal profiles were subsequently
averaged to provide mean temporal profiles for each
parameter for OH and control groups.
Evaluation of Autoregulation
Pressure-Flow Relationship
Regressions of BFV_M against MBP and BFV_S against SBP were
undertaken. We plotted BFV against BP for the entire time series
(during rest and 30-second averages during HUT) and fitted a linear
regression line. When R2
Autoregulatory Curve
In addition to an evaluation of the slope of the flow-BP curve,
we also obtained the BFV_M corresponding to the maximal fall of BP
during HUT to provide insights into the range of autoregulatory
responses to HUT. We constructed the autoregulatory curve for maximal
change of MBP (
Statistical Analysis
With HUT, the control group demonstrated a significant increase in HR
(P<.001) and DBP (P<.02) and fall in SV
(P=.001). In the OH group, HUT evoked a similar HR
increment. However, other systemic and cerebrovascular indices
responded quite differently. Compared with control subjects, there was
a significantly greater fall in PP (P<.001). OH patients
had a different pattern of systemic and cerebrovascular responses: BP
(SBP, DBP, MBP; P<.001) and TPR consistently fell
rather than rose (P<.02) during HUT; indices of cerebral
flow (BFV_D, BFV_M) and PF also declined significantly during HUT.
During HUT, CO was larger in OH patients, partially compensating for a
diminished cerebral blood flow, while other cardiac indices did not
change. CVR during HUT was significantly lower in OH patients than
control subjects (P<.001). Both groups showed a mild
reduction (<10%) of CO2 with HUT (P=NS between
groups). These data indicate that cerebral perfusion in the MCA
territory was compromised in patients with OH during HUT.
Hyperventilation
Autoregulation
Flow-Pressure Relationship
Change in BFV With Maximal MBP Decrement During HUT
Orthostatic Hypotension With Autoregulatory
Failure
A subgroup of five OH patients had autoregulatory failure (OH_AF),
as seen in Fig 3
Orthostatic Hypotension With Normal or Extended
Autoregulation
In this group of 16 OH patients, autoregulation was relatively
preserved, despite a large
To address the possible concern that the differences in slopes could be
related merely to the magnitude of
The symptoms of orthostatic intolerance are manifestations
of impaired cerebral perfusion resulting in cerebral hypoxia.
It is therefore paradoxical that attention has been focused almost
exclusively on cardiovascular indices of
orthostatic intolerance. Only limited information is
available on cerebral perfusion in the autonomic disorders. Within the
autoregulated range, a change in BP results in an insignificant change
in cerebral perfusion. Previous studies14 15 16 in patients
with OH have demonstrated an expansion of the autoregulated range at
both the upper and lower limits, so that cerebral perfusion remained
relatively constant with the patient in the supine position (when
supine hypertension might be present) and in response to standing
(when OH occurs). Some studies have additionally demonstrated that
cerebrovascular reactivity is dynamic. Changes in MCA MFV_M with HUT
with or without isoproterenol can precede alterations in
BP.17 18 The responses in orthostatically
symptomatic subjects18 and those who develop
postprandial hypotension19 appear to differ from those of
nonsymptomatic subjects. They may have a paradoxical
increase in CVR, as surmised from an increase in the pulsatility and
resistance indices. Also of interest is the observation that MCA
changes suggestive of ischemia can be induced with
hyperventilation in susceptible subjects.20
To establish the autoregulated range (within which a change in
pressure results in insignificant changes in flow) and the break points
above and below which flow changes with pressure, BP has been increased
by the infusion of an
As determined by regression analysis of response to HUT, three
patterns of response are evident in our patients with OH. No
correlation between flow and pressure was found in normal control
subjects and 8 of 21 patients with OH, confirming the presence of
intact autoregulation. These patients have an increased capacity to
cope with OH, since they have an expanded autoregulated range. A
similar group (n=8) exhibited failure of autoregulation but with a flat
flow-BP relationship. Only modest changes in BFV_M occurred in response
to the wide range of BPs that extended from supine hypertension to mild
OH at the beginning of HUT (<40 mm Hg), to maximal fall in BP at
the end of HUT in this group of OH patients (OH_NA). The third pattern
(OH_AF) was characterized by a "passive profile" of flow velocities
(BFV_M), which diminished in parallel with BP. As expected, a strong
positive flow-pressure correlation was found. These patients had a
steep BFV_M-MBP slope, so that even a mild reduction of MBP induced a
profound fall in BFV_M in these patients. All the OH patients
ultimately became symptomatic on HUT. For convenience, we
have combined the patients with completely preserved autoregulation
with those with autoregulatory failure but with a flat and expanded
"autoregulatory" curve. We think this approach is reasonable since
the patients with these two patterns have an increased capacity to cope
with OH compared with normal subjects. Our data emphasize the utility
of regression analysis. Specifically, we suggest that the
emphasis on dividing patients into those who autoregulate and those who
do not is less helpful than a quantitative description of the flow-BP
relationship. Patients with pattern 2 have autoregulatory failure and
hence no longer have break points, but because they have a flat curve,
they have enhanced tolerance of OH. In contrast, patients with pattern
3 (OH_AF) were characterized by mild OH and a steep flow-BP
relationship, indicating severe autoregulatory failure. These patients
develop cerebral hypoperfusion in response to small drops in BP. The
observation that the great majority of patients with OH have only mild
autoregulatory failure and a flat slope provides an explanation of why
modest improvements in BP result in dramatic improvements in symptoms.
The standing time before onset of presyncope, manifested as tilt
duration, was not different among patients within the three OH
subgroups, indicating that the results of cerebrovascular compensation
(as expanded autoregulation or autoregulatory failure with flat slopes)
enabled these patients to remain upright as long as patients with only
modest OH (and autoregulatory failure with steep slopes).
One limitation of the present analysis is that patients
with OH underwent greater MBP alterations than control subjects. The
study does not exclude the possibility that a modest regression might
exist in control subjects if large changes in BP were induced, ie,
simulating patients with mild autoregulatory failure with flat slopes.
A large error is improbable, since regression coefficient and slope
induced by small changes in BP in the OH group were similar to those
induced by large changes in MBP (not shown). The requirement of
R2
Adrenergic failure results in impaired vascular sympathetic innervation
and a fall in peripheral resistance during orthostasis.
With preserved myogenic and neurogenic autoregulation, cerebral
arterioles should respond to the elevated BP in the supine position by
vasoconstriction, thereby keeping flow constant. However, since at
least a part of cerebral autoregulation is neurogenic, central
sympathetic denervation would result in cerebral vessels passively
distending during the period of higher BP and assuming a smaller
caliber during OH. The fall in central resistance during HUT, in
parallel with the fall in peripheral resistance, suggests
that cerebral arterioles remain passively dilated and poorly responsive
to the BP changes.31 Thus, cerebrovascular vasomotor
reserve seems to be reduced with only a limited capacity to compensate
for changes in BP. Previous studies32 33 using the reactive
hyperemia test have also demonstrated that cerebral circulation
passively follows the rise and fall in BP in the supine position in
patients with multiple system atrophy and autonomic
failure.33 The possibility of a passive vasodilatation has
also been raised based on comparisons between MCA flow velocity and
133Xe washout measurements of cerebral blood flow in
patients with multiple system atrophy and autonomic failure during
45° HUT.16 Cerebral flow did not change, while a mild
reduction of MCA velocity (by 16%) was observed. Sensitivity to
CO2 and a capacity to vasodilate is usually preserved in
these patients.15 In our study,
vasoconstrictive response and CO2
sensitivity were tested as a response to CO2 reduction
during hyperventilation in the supine position. Indeed, for a similar
relative change of CO2, the vasomotor response and MCA flow
reduction were reduced in the OH patients, suggesting that some
impairment in the metabolic component of autoregulation
also existed.
In conclusion, the change in BP over a wide range from supine
hypertension to OH presents a significant challenge for the
regulation of cerebral perfusion. A range of autoregulatory responses
to changes in BP exists in patients with OH. The majority of patients
with OH have either normal or only mild autoregulatory failure, with
expansion of the "autoregulated" range, and develop symptoms only
with profound falls in BP. In approximately one in four patients, more
severe autoregulatory failure occurs, and cerebral hypoperfusion occurs
with relatively small change of BP. Cerebral hypoperfusion may place
the patient at significant risk to health and may cause injury.
Received July 8, 1997;
revision received October 9, 1997;
accepted October 9, 1997.
© 1998 American Heart Association, Inc.
Original Contributions
Autoregulation of Cerebral Blood Flow in Orthostatic Hypotension
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—We sought to
evaluate cerebral autoregulation in patients with
orthostatic hypotension (OH). 
BP <40 mm Hg;
R2>.75).
Key Words: autoregulation • cerebral blood flow • hypotension, orthostatic • ultrasonics
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Symptoms of OH such
as dizziness, lightheadedness, weakness, blurred vision, impairment of
concentration, and loss of consciousness occur when cerebral perfusion
is sufficiently impaired. Cerebral hypoperfusion develops when cerebral
autoregulation fails in the face of a severe reduction in BP. OH is
typically seen in generalized autonomic failure, as occurs in multiple
system atrophy and in the autonomic neuropathies such as diabetic
neuropathy.1 Although there is a positive
correlation between the fall in BP during HUT and symptoms of
orthostatic intolerance,2 patient complaints
can be vague or nonspecific. In addition, the obvious symptoms of OH,
such as lightheadedness or visual blurring, are often absent or delayed
in the elderly, where the main symptom is orthostatic
cognitive impairment in approximately 50% of patients.2
Therefore, an objective indicator of impaired cerebral perfusion is
needed. 
80 to 160 mm Hg SBP), cerebral
blood flow remains constant despite alterations in BP. In many patients
with chronic OH, MBP remains within the autoregulated range. Some
patients may also have an expansion of their autoregulated range so
that cerebral perfusion remains stable even when SBP falls to 60
mm Hg4 in the upright position. The aim of our study was
to evaluate the range of responses of cerebral perfusion to reduction
in BP and to attempt a quantitative evaluation of autoregulation, based
on the standardized stress of HUT.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Control Subjects and Patients
We studied 21 patients with neurogenic OH (9 men and 12 women;
mean age, 61.76±2.4 years [range, 52 to 78 years]). Eight patients
had been diagnosed with multiple system atrophy, 3 with pure autonomic
failure, 6 with diabetic neuropathy, and 4 with idiopathic
autonomic neuropathy. Neurogenic OH was considered to be
present if HUT induced a fall in SBP of 
30 mm Hg, DBP
10 mm Hg, or MBP 15 mm Hg, and an autonomic reflex
screen (to evaluate the severity and distribution of adrenergic,
sudomotor, and cardiovagal autonomic failure) confirmed generalized
autonomic failure. Autonomic failure was quantitated with the use of a
composite autonomic scoring scale5 (all patients scored 7
to 9 on the scale of 0 to 10, where 0=normal and 10=the most severe
autonomic failure). All our patients with multiple system atrophy and
pure autonomic failure fulfilled the criteria recommended by the
consensus panel.6 All patients were off regular medications
for at least 1 week before the studies, and insulin-dependent diabetic
patients were studied when under stable glycemic control.
Head-up Tilt
After an initial 10-minute resting period in the supine
position, the patient was tilted upright to an angle of 80° for 5 to
10 minutes and then returned to the supine position for an additional 5
minutes. HUT was interrupted if severe symptoms of
orthostatic intolerance occurred, whereupon the patient was
immediately returned to the supine position. Mean duration of tilt-up
was 8.0±2.1 minutes (range, 2 to 10.5 minutes).
After a 10-minute resting period, the patient was instructed to
breath at a frequency of two cycles per second for 4 minutes and then
allowed to breath at a comfortable spontaneous breathing frequency for
an additional 5 minutes.
Data Acquisition
Time series of consecutive HR, SBP, DBP, and respiration values
were continuously acquired. Beat-to-beat BP was measured from the
finger with the photoplethysmographic method (Finapres; Ohmeda
Monitoring Systems), which provides a reliable estimate of beat-to-beat
BP.7 BP was also measured in a standard way with the use of
a sphygmomanometer cuff.
With autoregulation, cerebral blood flow remains stable when BP
changes within the autoregulated range. In normal subjects, resting BP
is well within the autoregulated range, and changes in BP of 
30
mm Hg result in an insignificant change in BFV. In this situation no
significant correlation should exist between BP and BFV. To obtain
an estimate of the range of autoregulation or severity of its
impairment, we evaluated BPV responses to the larger changes in MBP
induced by HUT. The indices evaluated were as follows. .75, the regression
coefficient was also obtained. The coefficient of determination
(R2) provides an index of autoregulatory
failure, and the slope provides an index of the severity of such a
failure. These linear regressions were obtained over a large range of
BP changes from supine to standing in OH patients but over a more
narrow range in control subjects. MBP) in response to HUT and corresponding blood flow
values (BFV_M), accepting BFV_M as long as it did not exceed the
break point. Differences between rest and HUT were evaluated from time
profiles averaged over 30 seconds. The following formulas were
used: MBP=supine MBP-MBP minimum during HUT (30-second average) BFV_M=supine BFV_M-BFV_M at MBP minimum during HUT (30-second
average)
All parameters were compared before and after HUT in
OH patients and control subjects with the use of unpaired two-tailed
t tests13 and two-way ANOVA. We used a 2x2
contingency table (Fisher's exact test) to compare categorical
outcomes between control and OH groups. P<.05 was
considered significant. Data are presented as mean±SE.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Rest-Tilt Comparisons
The effect of HUT on the cardiovascular and
cerebrovascular hemodynamic indices is summarized in
Table 1
. Compared with the control group,
OH patients had higher resting supine heart rate (P=.007),
SBP (P=.03), DBP (P=.003), and MBP
(P=.008) than the control group, while blood flow velocities
(BFV_S, BFV_M, BFV_D), cardiovascular indices (SV, CO),
and TPR and CVR were not different.
View this table:
[in a new window]
Table 1. Mean Values of Cardiovascular and
TCD Parameters in Control Subjects and OH During HUT
Control subjects and OH patients underwent a similar reduction in
CO2 and HR in response to hyperventilation (Table 2). The control subjects, but not the OH
group, underwent significant hyperventilation-induced changes in
cerebral perfusion (BFV_S, BFV_M, BFV_D) and in CVR. Since the
reduction in CO2 was not different in OH patients compared
with control subjects, these data suggest that the vasoconstrictor
response to CO2 is reduced in OH patients.
View this table:
[in a new window]
Table 2. Mean Values of Cardiovascular and
TCD Parameters in Control Subjects and OH During
Hyperventilation
Fig 1 shows the temporal profiles of
MBP and BFV_M during rest and HUT in a normal control subject (A), an
OH patient with "preserved" autoregulation (B), and an OH patient
with autoregulatory failure (C). In the normal control subject, BP
increased and BFV_M remained stable during HUT (A). The flow-pressure
relationship failed to regress (Fig 1A, right panel). A large fall of
BP (>80 mm Hg) resulted in only a mild reduction of BFV_M in the
OH patient (B). The fall in BFV_M was modest relative to the fall in
BP, reflecting the flat flow-pressure slope (Fig 1B, right panel). In
contrast, autoregulatory failure, manifested as a large fall in BFV_M
for a relatively small BP reduction (<40 mm Hg), was seen in the
OH patient with autoregulatory failure (Fig 1C), reflecting the steep
flow-pressure curve (Fig 1C, right panel).
View larger version (25K):
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Figure 1. Time-averaged (30-second intervals) MBP and BFV_M
during rest; HUT and tilt-back are shown in the left-hand panels. On
the right is shown the flow-pressure relationship for the same patient.
A, Control subject. B, Patient with OH and preserved autoregulation
despite a large fall in BP (OH_NA). C, Patient with OH and
autoregulation failure (OH_AF).
We used regression analysis to test the hypothesis that
positive flow-pressure correlation and a linear flow-pressure
relationship can be predictive of autoregulation failure (see
"Evaluation of Autoregulation" in "Subjects and Methods").
Control subjects either did not have a significant positive correlation
of flow to pressure (13 of 14) or had a negative slope of regression (1
of 14). Negative slope indicates an increase in BP during HUT. In
contrast, 13 of 21 OH patients showed a significant correlation between
BFV_M and MBP (P=.0015, OH versus control, Fisher's exact
test). As shown in Fig 1
, no significant correlation was found in
control subjects (1A). In the OH patient with expanded autoregulatory
range (B), flow-pressure correlation was significant (r=.99)
with a relatively flat slope of regression (0.26). In contrast, high
correlation (r=.99) and a steep slope of regression (1.22)
were present in the OH patient with autoregulatory failure. The
slopes of the linear regressions for those OH patients with significant
coefficients of determination (R2>.75) are
plotted in Fig 2. When the coefficient of
determination was not significant, a default of 0 was accepted. Values
of 8 OH patients resembled control values, and 13 of 21 OH patients had
a positive slope, mostly (10 of 21) with slopes <1 cm/s per millimeter
of mercury.
View larger version (10K):
[in a new window]
Figure 2. Slopes of the regression curves for the 13 OH
patients with significant coefficients of determination
(R2>.75). A default value of 0 was assigned
if the coefficient of determination was not significant in control
subjects and 8 OH patients.
The relationship between BFV_M and maximal MBP in all
patients is shown in Fig 3. MBP in
control subjects ranged from -20 to 18 mm Hg and was associated
with an insignificant BFV_M. The OH group was separated into two
groups, the first with autoregulatory failure (OH_AF) and the second
with relatively preserved and often expanded autoregulation (OH_NA)
(Fig 3).
View larger version (17K):
[in a new window]
Figure 3. The flow-pressure relationship between rest and
HUT ( MBP vs MBP) for individual OH patients and control subjects,
using BFV_M corresponding to minimum MBP during HUT is shown (
indicates control subjects; 
, patients with OH and autoregulation
failure (OH_AF; n=5); 
, patients with OH and normal autoregulation
(OH_NA; n=16). Numbers indicate the slope of regression, if the
correlation coefficient was >.75.. The relationship between BFV_M and MBP of this
group was characterized by mild OH, large BFV_M, high correlation
coefficients, and steep flow-pressure regression slopes. MBP was
modest, ranging from 20 to 33 mm Hg. In contrast, the fall in
BFV_M was very large, ranging from 10 to 60 cm/s. The coefficients of
determination consistently exceeded 0.86, and the slopes of
individual BFV_M versus MBP linear regressions were positive, ranging
from 0.53 to 1.80 cm/s per millimeter of mercury. The reduction of
cerebral flow (BFV_M) was larger in the OH_AF patients than would be
predicted for a relatively small decline of BP. The BP reduction
(MBP) was lower in OH_AF than OH_NA patients (28.7±2.7 versus
46.9±5.6 mm Hg; P<.01). In contrast, cerebral flow
velocity (BFV_M) diminished more in the OH_AF (35.3±8.6 cm/s) than
in the OH_NA group (11.6±2.1 cm/s; P=.055). MBP ranging from 10.8 to 91.95
mm Hg. In response to this large MBP, BFV_M changed only
modestly, from -3 to 25 cm/s. Eight patients with mild OH (MBP
<40 mm Hg and modest BFV_M <15 cm/s) showed no correlation
between MBP and BFV_M, closely resembling control subjects. A
positive correlation between BFV_M and MBP was found in the
remaining 8 OH patients, who demonstrated severe OH (MBP 40 to
92 mm Hg). However, the slope of regression was flatter (<0.5)
than in the OH_AF group. The absolute minimum MBP was not different in
OH_NA (MBP 56.9±4.3 mm Hg) compared with the OH_AF patients (MBP
56.9±8.7 mm Hg). MBP in response to HUT, we
separately assessed BFV_M during the first 30 to 60 seconds of HUT,
which was associated with a smaller reduction of BP (MBP). At this
time MBP was <40 mm Hg in all OH patients. During this
period, when MBP was small, the OH-AF group was still easily
separable from the OH_NA group on the basis of BFV_M. For the OH_NA
group, the mean BFV_M in response to MBP of 28.9±3.8 mm Hg
was 7.57±1.2 cm/s, resulting in a slope of 0.26 cm/s per millimeter of
mercury, not significantly different from control values. In contrast,
the OH_AF group had a mean BFV_M response of 24.9±10.3 cm/s in
response to MBP of 16.2±5.1 mm Hg, resulting in a slope of
1.54 cm/s per millimeter of mercury, significantly steeper
(P<.001) than that of either control subjects or OH_NA. The
standing time (before tilt-back) was not different among these
subgroups of OH patients, despite large differences in MBP.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
There are three main findings of the present study. First, it
is possible to quantitate autoregulatory failure with the use of
regression analysis. Second, we make the novel finding that
patients with OH have three patterns of autoregulatory responses. One
group (n=8) has impaired autoregulation but with a flat flow-BP curve.
A second group (n=8) has intact autoregulation, with an expansion of
their autoregulated range. Group 3 (n=5) has a failure of
autoregulation, with a steep flow-BP curve. Patients with patterns 1
and 2 have an increased capacity to cope with OH, while those with
pattern 3 are greatly disadvantaged 
-agonist such as
angiotensin21 or
norepinephrine22 and reduced with
vasodilators23 or lower body negative
pressure.22 Other investigators have attempted to devise
approaches that do not require the infusion of vasoactive agents. These
include the transient hyperemic response that develops after
the release of ipsilateral carotid compression.24 25 The
response is akin to the MCA flow velocity changes that occur during
phase IV of the Valsalva maneuver. We chose a nonpharmacological method
of changing BP, since -agonists or antagonists, by their
direct action on arterioles, change the dependent (flow) as well as the
independent variable (BP).26 Tissues that autoregulate
have no, or only a weak, correlation of change in flow to corresponding
change in pressure. In contrast, tissues that do not autoregulate have
a linear or curvilinear relationship.26 27 28 The slope of
the relationship provides a quantitative description of the magnitude
of the failure. These observations are in agreement with the work of
Nelson et al,29 who described a linear relationship between
cerebral perfusion pressure and mean flow velocity below the
autoregulated range (break point). Kiel and Shepherd30 also
noted that the pressure-flow relationship became progressively more
linear with failure of autoregulation. .75 was selected because of the large
numbers of data points and the desire to accept only robust
regressions, in view of differences in MBP among the groups.
Selected Abbreviations and Acronyms
BFV
=
blood flow velocity
BFV_M
=
mean MCA flow velocity; BFV_M=BFV_D+BFV_PF/3 (cm/s)
BVF_PF
=
pulse flow; BFV_PF=BFV_S-BFV_D (cm/s)
BVF_D, BVF_S
=
diastolic, systolic MCA flow velocity (cm/s)
BFV_M=
average BFV_M during rest-BFV_M corresponding to minimum MBP during
tilt-up
BP
=
blood pressure (mm Hg)
CO
=
cardiac output; CO=SVxHR (L/min)
CVR
=
cerebrovascular resistance; CR=MBP/MFV (mm Hg/cm/s)
DBP, SBP
=
diastolic, systolic blood pressure (mm Hg)
HR
=
heart rate (beats per minute)
HUT
=
head-up tilt
MBP
=
mean blood pressure; MBP=DBP+PP/3 (mm Hg)
MBP=
average MBP during rest-minimum MBP during tilt (mm Hg)
MCA
=
middle cerebral artery
OH
=
orthostatic hypotension
OH_AF
=
OH patients with autoregulatory failure
OH_NA
=
OH patients with normal or expanded autoregulation
PP
=
pulse pressure; PP=SBP-DBP (mm Hg)
SV
=
stroke volume (mL)
TCD
=
transcranial Doppler sonography
TPR
=
total peripheral resistance; TPR=MBP/CO
(dyne.s/cm5)
Acknowledgments
This study was supported in part by grants from the National
Institute of Neurological Disorders and Stroke (PO1 NS32352), National
Aeronautics and Space Administration, and Mayo funds.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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