From the Department of Neurology (V.N., P.N.), Ohio State University,
Columbus, Ohio; and the Departments of Neurology (J.M.S., B.R.M., P.A.L.) and
Psychiatry (T.A.R.), Mayo Clinic, Rochester, Minnesota.
Correspondence to Phillip A. Low, MD, Department of Neurology, Mayo Clinic, 811 Guggenheim Bldg, 200 First St SW, Rochester, MN 55905. E-mail low.phillip{at}mayo.edu
Methods—Beat-to-beat BFV from the MCA, heart rate,
CO2, blood pressure (BP), and respiration were measured in
30 patients with OI (25 women and 5 men; age range, 21 to 44 years;
mean age, 31.3±1.2 years) and 17 control subjects (13 women and 4 men;
age range, 20 to 41 years; mean age, 30±1.6 years); ages were not
statistically different. These indices were monitored during supine
rest and head-up tilt (HUT). We compared spontaneous breathing and
hyperventilation and evaluated the effect of CO2
rebreathing in these 2 positions.
Results—The OI group had higher supine heart rates
(P<0.001) and cardiac outputs (P<0.01)
than the control group. In response to HUT, OI patients underwent a
greater heart rate increment (P<0.001) and greater
reductions in pulse pressure (P<0.01) and
CO2 (P<0.001), but total systemic
resistance failed to show an increment. Among the cerebrovascular
indices, all BFVs (systolic, diastolic, and mean)
decreased significantly more, and cerebrovascular resistance (CVR) was
increased in OI patients (P<0.01) compared with control
subjects. In both groups, hyperventilation induced mild
tachycardia (P<0.001), a significant
reduction of BFV, and a significant increase of CVR associated with a
fall in CO2. Hyperventilation during HUT reproduced
hypocapnia, BFV reduction, and tachycardia and
worsened symptoms of OI; these symptoms and indices were improved
within 2 minutes of CO2 rebreathing. The relationships
between CO2 and BFV and heart rate were well described by
linear regressions, and the slope was not different between control
subjects and patients with OI.
Conclusions—Cerebral vasoconstriction occurs in OI during
orthostasis, which is primarily due to hyperventilation, causing
significant hypocapnia. Hypocapnia and symptoms
of orthostatic hypertension are reversible by
CO2 rebreathing.
This study was designed to evaluate cerebral vasoregulation in patients
with orthostatic intolerance (OI) during HUT. The objective
was to evaluate whether paradoxical cerebral vasoconstriction occurred
in OI and its mechanism. We hypothesized that cerebral hypoperfusion
might be related to changes in CO2, which has a
predictable effect on cerebral perfusion. Therefore, we undertook a
series of studies to evaluate the effect of HUT on respiration,
CO2 cerebral blood flow, and systemic
cardiovascular peripheral responses in OI
patients and healthy control subjects. We also evaluated the effect of
correction of CO2 on the recorded
abnormalities and symptoms of orthostatic intolerance.
Protocols
Head-Up Tilt
Hyperventilation
CO2 Rebreathing
Data Acquisition and Analysis
Transcranial Doppler Testing
Impedance Cardiography
Respiration and CO2
Statistical Analysis
Head-Up Tilt
In control subjects, respiratory frequency and
CO2 did not significantly change during HUT. In
contrast, OI patients underwent a significant degree of
hypocapnia during HUT (P<0.01). Mean
respiratory frequency for the OI group during HUT (0.25 Hz) did not
differ significantly from that of the control group (0.23 Hz), although
the range of respiratory frequencies was wider during HUT in the OI
group (from 0.06 to 0.39 Hz) than in the control group (0.12 to 0.31
Hz). In OI patients, spontaneous rhythmic breathing was interrupted by
episodes of deep breaths, faster respiratory rate, irregular
respiration, or apneas. We have not quantified these differences.
Hyperventilation
Vasomotor Sensitivity to CO2
To quantify the relationship between CO2 and BFV
and heart rate, we used linear regression to compare changes in
CO2 to changes in BFVM and
heart rate in patients with OI who participated in this protocol and
control subjects. BFVM correlated significantly
with the level of CO2 subjects with
coefficient of determination >0.8 (P<0.0001) in all
patients. Linear regression was used to quantify the relationship. For
OI, the relationship between BFVM and
CO2 had a coefficient of determination of 0.93,
and the slope was 1.46 (Figure 3A
The main findings in this study were that symptoms of
orthostatic intolerance in this group of patients were
associated with cerebral hypoperfusion and increased CVR. This
paradoxical cerebrovascular arteriolar vasoconstriction is caused by
hypocapnia and can be reversed by CO2
rebreathing. The improvement in cerebral perfusion was associated with
resolution of symptoms.
We need to address the sources of error in the use of the Finapres to
measure beat-to-beat BP, impedance cardiography for measuring indices
of preload and afterload, and TCD ultrasonography for measuring
cerebral blood flow. Finapres measures digital arterial
pressure using a volume clamp method11 from the
digital artery of the index finger. SBP-, DBP-, and MBP-recorded
pressures measured using the Finapres compare accurately with
simultaneous brachial and radial intra-arterial
recordings11 and reproduce the
continuously changing intra-arterial waveform during the
Valsalva maneuver12 and during sudden changes in
posture.11 Determinations of CO using the
thoracic electrical bioimpedance technique have been found to correlate
strongly with results from indicator or thermodilution measurements
taken with indwelling catheters,13 and this
technology tracks changes in SV and CO very
reliably,13 including beat-to-beat changes of
left ventricular SV from simultaneous left
ventriculograms. These techniques accurately measure relative changes
in a wide range of conditions. MCA flow velocity correlates with
cerebral blood flow, measured with xenon clearance
techniques14 or with laser Doppler
flux15 and flow velocity estimates. Flow velocity
can increase because of an increased flow through the arterioles distal
to the probe or a constriction of the insonated trunk. Changes of the
caliber of MCA stem (the insonated segment in TCD) in response to BP
and CO2 are small
(<4%).16 Larger changes in trunk caliber can
occur, but only under extreme circumstances such as
subarachnoid hemorrhage or injury to the vessel.
During HUT, heart rate increment, reduction of cerebral BFV, and
increase of CVR strongly correlated with end-tidal
CO2. This hypocapnia was associated
with symptoms of lightheadedness and weakness. Correction of
hypocapnia during CO2 rebreathing in
an upright position reduced orthostatic
tachycardia and normalized cerebral BFV, and the symptoms
of orthostatic intolerance abated. During hyperventilation
in the supine position, none of the cerebral blood flow and resistance
indices differed between the OI patient group and the control group.
Additionally, the slope of the regression line relating BFV to
CO2 was not different when the OI group was
compared with the control group. These data suggest that vasomotor
reactivity is preserved in OI patients.
A key question is why hypocapnia occurs in OI
patients. The hyperventilation syndrome per se is not a psychiatric
diagnosis but is often associated with anxiety, depression, and panic
attacks.17 We need to ask whether these patients
develop hyperventilation because HUT evokes orthostatic
anxiety or panic attacks or whether there is a
physiological basis for their
orthostatic hyperventilation. Hyperventilation is
associated with a variety of symptoms that overlap with those of OI.
These include cardiac (palpitations, chest pain), neurological
(dizziness, syncope, paresthesias, tetany), and psychiatric (feeling of
unreality, intense fear, hallucinations, euphoria) symptoms. As with OI
and POTS, the hyperventilation syndrome is more prevalent in women.
This syndrome is associated with cerebral vasoconstriction, resulting
in dizziness, vision disturbance, and, often, paresthesias;
with a reduction of up to 60% of BFV; and with a concomitant increase
of spectral powers in slower rhythms on the electroencephalograph that
are suggestive of ischemia.18 A recent
study of 85 subjects attempted to segregate the contributions of
anxiety and somatic manifestations to symptoms associated with
hyperventilation. Anxiety was considered to explain approximately 30%
of symptoms, whereas somatic symptoms such as cardiac symptoms,
dizziness, and fainting correlated with reduced
CO2.19
However, there are some significant differences between POTS and
the hyperventilation syndrome. The respiratory rate and end-tidal
CO2 in POTS with the patient at rest are
identical to those of control subjects. Hyperventilation that consists
of an increased depth without an increased rate only occurs during
orthostatic stress. Patients increase their depth of
respiration after they develop a transient reduction in BP and a
persistent reduction in pulse pressure. An increase in respiratory
depth is a well-known mechanism that results in an increase in BP by
increasing preload mechanically and by
venoconstriction.20 Deep inspiration also
activates a vasoconstrictor reflex with a spinal
pathway.21 Finally, respiratory neurons modulate
the rostral ventrolateral medulla and hence vasomotor
tone.22
Our tentative position is that OI and anxiety-panic states share
a common efferent pathway involving sympathetic activation but that
they are evoked by quite different mechanisms. Evidence exists to
implicate the noradrenergic system in the development
of the anxiety-panic state.23 Even small
alterations in noradrenergic function can produce
significant cardiovascular, gastrointestinal, and
respiratory symptoms in patients with panic disorder that are similar
to symptoms experienced by patients with OI. However, the mechanisms
evoking those similar symptoms appear to be quite different. OI
patients hyperventilate as a compensatory response to OI. However,
continued hyperventilation is counterproductive because it causes
hypocapnia, which induces a reduction in cerebral
perfusion, and worsens symptoms of OI. Furthermore, although a single
breath will transiently increase, continued hyperventilation reduces
total systemic peripheral resistance, further aggravating
OI. For individuals with panic disorder, changes in respiratory rate
(ie, hyperventilation) produce panic symptoms rather than being a
compensatory phenomenon as seen in patients with OI. Hyperventilation
produces hypocapnia and precipitates panic symptoms in
individuals with panic disorders. However, hypercapnia has also been
associated with the induction of panic. The reason why hypo- and
hypercapnia both produce panic symptoms is
unclear,24 and this raises the question of
whether POTS patients are unduly sensitive to hypocapnia.
We found no difference in the slope between heart rate and BFV
responses to changes in PCO2 in OI
patients and control subjects (Figure 3
Although the focus of this article is on the contributions of
hypocapnia to cerebral hypoperfusion, it is clear that
there are also changes that occur at rest in OI patients. They have a
higher resting heart rate, CO, and TPR than control subjects. These
findings are in keeping with a hyperadrenergic state causing
peripheral vasoconstriction and an increase in heart rate
and CO. There is also heterogeneity in mechanisms in
these patients. In the present study, we demonstrated the failure
of TPR to vary incrementally with HUT. In an earlier
study,25 we demonstrated that POTS patients who
had a tendency toward syncope have a progressive decrease in TPR,
whereas another group (who tend not to faint) have a normal or higher
TPR with HUT. With the patient supine, a part of the
peripheral vasoconstriction is in the veins, which show
denervation supersensitivity26 ; these same veins
fail to maintain their tone with the patient standing, resulting in
venous pooling.27
In summary, patients with OI respond to HUT-induced
cardiovascular alterations with an increased depth of
respiration, which augments the oscillations in BP. This in
turn results in hypocapnia and cerebral hypoperfusion,
worsening OI.
Received February 20, 1998;
revision received June 23, 1998;
accepted June 23, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Hypocapnia and Cerebral Hypoperfusion in Orthostatic Intolerance
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and
Purpose—Orthostatic and other stresses trigger
tachycardia associated with symptoms of tremulousness,
shortness of breath, dizziness, blurred vision, and, often, syncope. It
has been suggested that paradoxical cerebral vasoconstriction during
head-up tilt might be present in patients with
orthostatic intolerance. We chose to study middle cerebral
artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation
during tilt in patients with orthostatic intolerance
(OI).
Key Words: hypotension, orthostatic • hypocapnia • hypoperfusion • orthostatic intolerance • ultrasonography, Doppler, duplex
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Orthostatic intolerance is characterized by symptoms of
lightheadedness, tiredness, palpitations, blurred vision, and,
occasionally, by loss of consciousness during standing, all of which
are relieved on recumbency.1 Previous studies
suggested that mild peripheral autonomic
neuropathy affecting sudomotor and adrenergic fibers is
associated with excessive orthostatic
tachycardia.1 2 3
Orthostatic symptoms are predominantly those of cerebral
hypoperfusion, and they occur in the absence of orthostatic
hypotension. Cerebral autoregulation maintains constant cerebral blood
flow despite changes in systemic blood pressure (BP). There is some
evidence that disorders associated with orthostatic
intolerance may also have impaired autoregulation. Previous studies
have suggested that abnormal cerebral vasoreactivity is found in
patients with vasodepressor syncope.4 5 A fall of
blood flow velocity (BFV) in the middle cerebral artery (MCA) preceded
the onset of syncope with rapid reduction of BP, during lower body
negative pressure testing.4 5 Similarly, an
increase in the cerebrovascular resistance (CVR) preceded the onset of
syncope during head-up tilt (HUT).6 7 These
studies suggested that paradoxical vasoconstriction is overriding
the results of autoregulatory vasodilation, causing a rightward
shift on the autoregulatory curve.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Subjects
Thirty patients suffering from OI and 17 healthy subjects
participated in the study. Inclusion criteria required (1) sinus rhythm
with no evidence of arrhythmia or cardiac disease; (2) heart
rate increment >30 beats per minute (bpm) from the baseline and >100
bpm for >60% of the duration of the 10-minute tilt-table test; (3)
stable BP profile without syncope, presyncope, or
orthostatic hypotension; and (4) the presence of 3 or more
of the following clinical symptoms for at least 3 months: dizziness,
fatigue, palpitations, blurred vision, breathing difficulties, abnormal
sweating, nausea, gastrointestinal dysmotility, headache. Patients were
excluded if they received medications that could cause OI, if they were
hypovolemic due to blood volume or fluid loss, or if they suffered from
any medical condition that was known to cause OI (such as diabetes or
peripheral neuropathy). Detailed clinical
evaluation included a general medical, cardiological, and neurological
history; physical examination; and laboratory evaluation. The
evaluation typically included Holter monitoring, determination of
plasma volume, determination of catecholamine level,
thyroid function testing, electroencephalography,
electrocardiography, and MRI or CT head
scanning, if indicated. No cardiac or other pathology that could
explain episodes of tachycardia and OI was found. All
medications were withheld for 5 half-lives before autonomic testing.
None of the patients used cardioactive or anticholinergic medication.
All patients and subjects refrained from tobacco and caffeine use on
the day of the study.
In protocol 1, the patients (n=22) performed the Valsalva
maneuver and underwent hyperventilation in the supine position. After a
period of rest, they underwent HUT. Eight of the patients also
participated in protocol 2, in which they underwent hyperventilation
after HUT, followed by rebreathing of CO2 in an
upright position.
After 10 minutes of rest in the supine position, the patient
underwent HUT to 80° for 10 minutes and then was returned to the
supine position for a further 5 minutes.
After 10 minutes of rest in the supine position, the patient was
instructed to hyperventilate at a frequency of 1 Hz for 4 minutes and
then to breathe quietly and spontaneously.
After 5 minutes of rest, the patient was tilted up to an angle
of 80° and underwent 4 minutes of hyperventilation to induce
hypocapnia. The patient then underwent
CO2 rebreathing for 5 minutes or until
CO2 returned to baseline values. During
CO2 rebreathing, the patients maintained
spontaneous breathing frequency, inhaling and exhaling from a 1500-mL
rebreathing bag. ECG, BP, respiration, and CO2
were measured continuously at 250 Hz, simultaneous with the
transcranial Doppler (TCD) signal.
Time series of R-R intervals, systolic (SBP), and
diastolic (DBP) BP were measured beat to beat. Heart rate
was calculated from R-R intervals. BP was measured via the finger using
the photoplethysmographic method (Finapres; Ohmeda Monitoring
Systems), which provides a reliable estimate during both short-
and long-term recordings of intra-arterial
BP.8 9 Respiratory and CO2
signals were equidistantly sampled at 4 Hz.
Cerebral BFV was measured using the Transcranial
Doppler System (Multigon Industries). The left MCA was insonated
from the anterior temporal window. A TCD probe (2 MHz) was positioned
to record the maximal MCA velocity and fixed in the desired angle
using a specially designed Teflon probe holder. The envelope of maximal
BFV is similar to the BP waveform. Systolic
(BFVS), diastolic
(BFVD), and mean (BFVM)
BFVs were detected from analog signals on a beat-to-beat basis. CVR was
defined as mean blood pressure (MBP)/BFVM.
Changes in thoracic impedance during the cardiac cycle largely
reflect changes in thoracic aortic volume and hence in left
ventricular outflow.10 All subjects
were tested using an impedance plethysmograph (Bomed
NCCOM3 R-7), had normal cardiovascular function, and
were free of intraventricular conduction defects,
intracardiac shunts, or valvular insufficiency that may
confound stroke volume (SV) and cardiac output (CO) measurements. The
equation for calculation of SV and CO used adjustments for the body
surface area, which may account for interindividual variation of the
impedance estimate. SV and CO were also acquired beat to beat,
simultaneous with other signals.
Respiratory excursion was measured using a nasal thermistor and
sampled at 4 Hz. CO2 was measured from the
expiratory flow using a Puritan-Bennett 254 airway gas monitor
calibrated with 5% CO2. All data were
simultaneously acquired; outlying values and extrasystoles
were carefully removed. Time series were then averaged over 30-second
intervals for each parameter to obtain individual temporal
profiles; group averaged profiles were also obtained.
For comparison of groups, unpaired 2-tailed t test
was used. When a comparison of multiple groups was made, we used ANOVA
with a repeated-measure design and Scheffé's test was used for
post hoc analysis. Statistical analysis of sex
distribution was done using 
2 with
Yates correction and 2x2 contingency table . The relationships of
BFVM to CO2 and heart rate
to CO2 were evaluated using linear regression
analysis. Data was expressed as mean±SEM, and significance was
accepted at the 5% level.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Clinical Characteristics
Sex and age distributions of patients (25 women and 5 men;
age range, 21 to 44 years; mean age, 31.3±1.2 years) and healthy
control subjects (13 women and 4 men; age range, 20 to 41 years; mean
age, 30±1.6 years) were not statistically different. All patients
experienced typical symptoms of OI such as dizziness, lightheadedness,
and fatigue. None of the healthy control subjects reported symptoms of
OI during HUT.
In all orthostatically intolerant patients, supine
heart rate (P<0.001) and cardiac output
(P<0.01) were greater than in the control group (Table 1
). BP, BFV,
end-diastolic volume, total peripheral
resistance (TPR), and CVR for the OI patient group were not different
from those of the control group during supine rest. Figure 1 shows the mean average temporal profile
of all variables in the OI and control groups during HUT (Figure 1). Data for each subject were reduced to 30-second averages, and the
mean averages were obtained and displayed for each group for visual
clarity. In response to HUT, compared with control subjects, OI
patients had significantly higher heart rates (P<0.001),
greater COs (P<0.001), and lower pulse pressures
(P<0.05) and CO2 levels
(P<0.01) (Table 1, Figure 1). Among the cerebrovascular
indices, all MCA BFVs (BFVS, P<0.05;
BFVD, P<0.05;
BFVM, P<0.05; and pulse
[BFVP], P<0.05) were also
significantly lower during HUT in the patients with OI. In contrast,
CVR increased during HUT in OI patients (P<0.01) but not in
control subjects. TPR significantly increased with HUT in control
subjects (P<0.05) but not in patients with OI, and TPR
values during HUT were lower (P<0.01) in OI patients than
in control subjects. EDV, an index of preload, was not different
between groups either in the supine position or during HUT. HUT
resulted in the following symptoms: lightheadedness, palpitations,
weakness, and, less commonly, chest aching and acral paresthesias.
View this table:
[in a new window]
Table 1. Cardiovascular and TCD Parameters in Control
Subjects and OI Patients During
HUT
View larger version (23K):
[in a new window]
Figure 1. Temporal profile of group-averaged values from OI
patients (left) during rest, tilt-up, and posttilt of heart rate (HR),
mean blood pressure (MBP), mean blood flow velocity (BFV_M), pulse
blood flow velocity (pulse flow), pulse pressure,
CO2, TPR, and CVR. Corresponding profile of group-averaged
values from control subjects is shown in the right panel.
During supine rest, OI patients had higher heart rates
(P<0.001). In both groups, hyperventilation induced mild
tachycardia (P<0.001), a significant reduction
of BFV (BFVS, BFVD, and
BFVM), and a significant increase in CVR
(Table 2); TPR was
significantly reduced in the control subjects. Hyperventilation
significantly increased CO in control subjects (P<0.05) but
not in OI patients.
View this table:
[in a new window]
Table 2. Cardiovascular and TCD Parameters in Control
Subjects OI Patients During
Hyperventilation
Vasomotor sensitivity was evaluated during protocol 2 (HUT with
hyperventilation and CO2 rebreathing) in OI
patients. HUT with hyperventilation induced significant reductions of
MCA BFV and CO2 and a significant increase in
heart rate and CVR. BP was not significantly different. The symptoms of
OI were more severe during HUT with hyperventilation. The indices of
cerebral perfusion (MCA BFV and CVR) rapidly improved within the first
2 minutes of CO2 rebreathing, and all abnormal
indices were significantly improved (Table 3). Heart rate was lower
during CO2 rebreathing, and symptoms of OI
improved. BP was not significantly different. Figure 2 shows the typical profile of heart
rate, BFVM, MBP, and CO2
from 1 patient.
View this table:
[in a new window]
Table 3. HUT With Hyperventilation and CO2
Rebreathing
View larger version (19K):
[in a new window]
Figure 2. Temporal profile of beat-to-beat heart rate (HR),
mean blood pressure (MBP), and mean flow velocity (BFV_M) data from 1
patient (23-year-old woman with OI) during HUT with hyperventilation
and CO2 rebreathing. There is a significant reduction of
BFVM during tilt, with hyperventilation accompanied by
tachycardia. HR and BFVM improved during tilt
with CO2 rebreathing. The first arrow indicates HUT and
commencement of hyperventilation; the second arrow, rebreathing of
CO2; and the third arrow, tilt-back. ). A
significant regression was also found between heart rate and
CO2; coefficient of determination was 0.86, and
slope was -0.54. Corresponding values for the control group
BFVM versus CO2 slopes were
R2=0.86, P<0.001; heart rate
versus CO2, R2=0.72,
P<0.0001. There was no significant difference between the
slope for patients with OI and that of the control subjects.
View larger version (18K):
[in a new window]
Figure 3. Regression of mean blood flow velocity (BFV_M) vs
CO2 (A) and heart rate (HR) vs CO2 (B) of
30-second averages from patients with OI ( 
) and controls (
)
during HUT with hyperventilation and CO2 rebreathing.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We originally defined "postural tachycardia
syndrome" (POTS) as an increase in heart rate exceeding 30 bpm
associated with orthostatic symptoms. We subsequently found
that this definition included a rather heterogeneous group
of patients, including patients with deconditioning, POTS, and
constitutional OI. We subsequently redefined POTS as "requiring an
orthostatic heart rate 
120 bpm."2
When we used this definition, not all of our patients qualified, so we
chose the more inclusive term of OI for this article. 
), indicating that
supersensitivity is not present.
Acknowledgments
This study was supported in part by grants from NINDS (PO1
NS32352) and NASA and by Mayo Clinic funds.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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T. Laitinen, L. Niskanen, G. Geelen, E. Lansimies, and J. Hartikainen Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects J Appl Physiol, June 1, 2004; 96(6): 2333 - 2340. [Abstract] [Full Text] [PDF]
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 J. Gisolf, R. Wilders, R. V. Immink, J. J. van Lieshout, and J. M. Karemaker Tidal volume, cardiac output and functional residual capacity determine end-tidal CO2 transient during standing up in humans J. Physiol., January 15, 2004; 554(2): 579 - 590. [Abstract] [Full Text] [PDF]
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 D. A. Cowie, J. K. Shoemaker, and A. W. Gelb Orthostatic Hypotension Occurs Frequently in the First Hour After Anesthesia Anesth. Analg., January 1, 2004; 98(1): 40 - 45. [Abstract] [Full Text] [PDF]
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 V. Novak, A. Chowdhary, B. Farrar, H. Nagaraja, J. Braun, R. Kanard, P. Novak, and A. Slivka Altered cerebral vasoregulation in hypertension and stroke Neurology, May 27, 2003; 60(10): 1657 - 1663. [Abstract] [Full Text] [PDF]
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J. J. Van Lieshout, W. Wieling, J. M. Karemaker, and N. H. Secher Syncope, cerebral perfusion, and oxygenation J Appl Physiol, March 1, 2003; 94(3): 833 - 848. [Abstract] [Full Text] [PDF]
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 C. Schroeder, J. Tank, M. Boschmann, A. Diedrich, A. M. Sharma, I. Biaggioni, F. C. Luft, and J. Jordan Selective Norepinephrine Reuptake Inhibition as a Human Model of Orthostatic Intolerance Circulation, January 22, 2002; 105(3): 347 - 353. [Abstract] [Full Text] [PDF]
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 A. G. Hermosillo, K. Jauregui-Renaud, A. Kostine, M. F. Marquez, J. L. Lara, and M. Cardenas Comparative study of cerebral blood flow between postural tachycardia and neurocardiogenic syncope, during head-up tilt test Europace, January 1, 2002; 4(4): 369 - 374. [Abstract] [PDF]
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A. Lagi, S. Cencetti, V. Corsoni, D. Georgiadis, and S. Bacalli Cerebral Vasoconstriction in Vasovagal Syncope: Any Link With Symptoms?: A Transcranial Doppler Study Circulation, November 27, 2001; 104(22): 2694 - 2698. [Abstract] [Full Text] [PDF]
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J. K. Shoemaker, D. D. O'Leary, and R. L. Hughson PETCO2 inversely affects MSNA response to orthostatic stress Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1040 - H1046. [Abstract] [Full Text] [PDF]
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J. J. van Lieshout, F. Pott, P. L. Madsen, J. van Goudoever, and N. H. Secher Muscle Tensing During Standing : Effects on Cerebral Tissue Oxygenation and Cerebral Artery Blood Velocity Stroke, July 1, 2001; 32(7): 1546 - 1551. [Abstract] [Full Text] [PDF]
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 M. Lamarre-Cliche and J. Cusson The fainting patient: value of the head-upright tilt-table test in adult patients with orthostatic intolerance Can. Med. Assoc. J., February 1, 2001; 164(3): 372 - 376. [Abstract] [Full Text] [PDF]
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T. T. Schlegel, T. E. Brown, S. J. Wood, E. W. Benavides, R. L. Bondar, F. Stein, P. Moradshahi, D. L. Harm, J. M. Fritsch-Yelle, and P. A. Low Orthostatic intolerance and motion sickness after parabolic flight J Appl Physiol, January 1, 2001; 90(1): 67 - 82. [Abstract] [Full Text] [PDF]
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 J. Jordan, J. R. Shannon, A. Diedrich, B. Black, F. Costa, D. Robertson, and I. Biaggioni Interaction of Carbon Dioxide and Sympathetic Nervous System Activity in the Regulation of Cerebral Perfusion in Humans Hypertension, September 1, 2000; 36(3): 383 - 388. [Abstract] [Full Text] [PDF]
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 J. R. Shannon, N. L. Flattem, J. Jordan, G. Jacob, B. K. Black, I. Biaggioni, R. D. Blakely, and D. Robertson Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency N. Engl. J. Med., February 24, 2000; 342(8): 541 - 549. [Abstract] [Full Text] [PDF]
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