| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vol. 83, Issue 6, 2139-2145, December 1997
Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, and University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75231
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Zhang, Rong, Julie H. Zuckerman, James A. Pawelczyk, and
Benjamin D. Levine. Effects of head-down-tilt bed rest on cerebral
hemodynamics during orthostatic stress. J. Appl.
Physiol. 83(6): 2139-2145, 1997.
Our aim was to
determine whether the adaptation to simulated microgravity (µG)
impairs regulation of cerebral blood flow (CBF) during orthostatic
stress and contributes to orthostatic intolerance. Twelve
healthy subjects (aged 24 ± 5 yr) underwent 2 wk of 
6°
head-down-tilt (HDT) bed rest to simulate hemodynamic changes that
occur when humans are exposed to µG. CBF velocity in the middle
cerebral artery (transcranial Doppler), blood pressure, cardiac output
(acetylene rebreathing), and forearm blood flow were measured at each
level of a ramped protocol of lower body negative pressure (LBNP;
15, 30, and 40 mmHg × 5 min, 50 mmHg × 3 min, then 10 mmHg every 3 min to presyncope) before
and after bed rest. Orthostatic tolerance was assessed by using the
cumulative stress index (CSI; mmHg × minutes) for the LBNP
protocol. After bed rest, each individual's orthostatic tolerance was
reduced, with the group CSI decreased by 24% associated with greater
decreases in cardiac output and greater increases in systemic vascular
resistance at each level of LBNP. Before bed rest, mean CBF velocity
decreased by 14, 10, and 45% at 40 mmHg, 50 mmHg, and
maximal LBNP, respectively. After bed rest, mean velocity decreased by
16% at 30 mmHg and by 21, 35, and 39% at 40 mmHg,
50 mmHg, and maximal LBNP, respectively. Compared with pre-bed
rest, post-bed-rest mean velocity was less by 11, 10, and 21% at
30, 40, and 50 mmHg, respectively. However, there
was no significant difference at maximal LBNP. We conclude that
cerebral autoregulation during orthostatic stress is impaired by
adaptation to simulated µG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of
cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.
microgravity; blood flow; orthostasis; Doppler
INTRODUCTION ALTHOUGH ORTHOSTATIC INTOLERANCE is a frequent
consequence of the cardiovascular adaptation to microgravity or
ground-based simulations such as bed-rest deconditioning, the
underlying mechanisms remain unclear (7, 18, 30). Most hypotheses focus
on blood pressure regulation and include deconditioning-related
hypovolemia (30); changes in cardiovascular mechanics (19, 21);
compromised ability to increase total peripheral resistance (7); and
impairment of baroreflex regulation of heart rate (9, 11). However, syncope during orthostatic stress ultimately occurs because of a
reduction in cerebral blood flow (CBF) sufficient to cause loss of
consciousness.
There are two mechanisms by which this process may occur. The first and
most commonly accepted hypothesis is that the fall in CBF is secondary
to systemic hemodynamic collapse (4). Alternatively, we and others have
suggested that there may be a cerebral vasoconstriction associated with
a primary impairment of cerebral autoregulation that may compromise CBF
during orthostatic stress (6, 14, 19). Contrary to what might be
predicted from the traditional concept of cerebral
autoregulation, we observed a decrease in mean CBF velocity during
graded lower body negative pressure (LBNP) despite maintenance of mean
arterial pressure. Furthermore, in subjects who were prone to syncope
during LBNP, decreases in CBF velocity occurred earlier at lower levels
of LBNP than in those subjects who regulated arterial pressure more
successfully. These results suggested that impairment of cerebral
autoregulation may contribute to orthostatic intolerance (19).
Prolonged head-down-tilt (HDT) bed rest has been used to simulate
hemodynamic changes that occur when humans are exposed to microgravity
and often results in orthostatic intolerance (5, 7). We conducted the
present study to determine the effects of simulated microgravity on
cerebral hemodynamics during orthostatic stress. We hypothesized that a
decrease in CBF velocity would be observed at lower levels of LBNP
after bed rest, associated with a reduction in orthostatic tolerance.
Furthermore, we speculated that these changes also would be associated
with an increase in the correlation between variations in arterial
pressure and CBF velocity, indicating an increased dependence of flow
velocity on changes in pressure and impairment of cerebral
autoregulation.
METHODS
6° HDT. Subjects were allowed to
raise up on one elbow for meals but otherwise were restricted to the head-down position at all times. Subjects were housed in the General Clinical Research Center at the University of Texas Southwestern Medical Center and given a standard diet consisting of 2,827 ± 609 cal/day, including 5.2 ± 1.2 gm/day of sodium. Fluids
were allowed ad libitum, but all fluid intake and urine output were carefully recorded. All experiments were repeated after 18 days of HDT.
Orthostatic stress.
Progressive LBNP was used to decrease central blood volume in a graded
fashion and facilitate physiological evaluation during orthostatic
stress. Subjects were placed in a Plexiglas LBNP box that was sealed at
the level of the iliac crests. Suction was provided by a vacuum pump
and controlled with a variable autotransformer. Pressure differential
between the chamber and atmosphere was measured with a mercury
manometer. After at least a 30-min baseline period of quiet rest, the
magnitude of the suction was increased in a stepwise fashion according
to the following protocol: 15 mmHg × 5 min, 30 mmHg × 5 min, 40 mmHg × 5 min, 50 mmHg × 3 min, and increasing negative pressure increments by 10 mmHg
every 3 min to the point of maximal tolerance. LBNP was discontinued if
the subject developed signs and/or symptoms of presyncope: sudden onset of nausea, sweating, light headedness, bradycardia, or
hypotension (sustained systolic blood pressure <80 mmHg). Orthostatic tolerance was assessed by using the cumulative stress index, calculated as the sum of the products of the duration of LBNP and the magnitude of
the negative pressure at each level (mmHg × minutes).
Data acquisition.
All experiments were performed in the morning, at least 2 h after a
light breakfast, and >12 h after the last caffeinated beverage or
alcohol, in a quiet, environmentally controlled laboratory, with an
ambient temperature of 22 ± 1°C. Heart rate was continuously monitored by electrocardiography (Hewlett-Packard), and beat-to-beat blood pressure was measured in the finger by photoplethysmography (Finapres, Ohmeda). Intermittent blood pressure was measured in the arm
by electrosphygmomanometry (Suntech) with a microphone placed over the
brachial artery and the Korotkoff sounds gated to the
electrocardiograph.
Cardiac output was measured with a standard foreign gas rebreathing
technique by using acetylene as the soluble and helium as the insoluble
gas. Adequate mixing of the rebreathing gas in the lung was confirmed
by a constant level of helium in all cases. This technique has been
described previously and has been validated against both indocyanine
dye and thermodilution methods in healthy subjects and in patients with
significant cardiopulmonary disease (16, 27, 29). Cardiac output was
measured at baseline and at each level of LBNP up to 40 mmHg,
then measured at every other level of LBNP to allow at least 5 min for
the inhaled acetylene to be cleared after the previous measurement.
Mean arterial pressure obtained during the rebreathing was divided by
cardiac output to calculate systemic vascular resistance.
Forearm blood flow was measured by using venous occlusion
plethysmography. A mercury-in-Silastic strain gauge was placed over the
largest part of the subject's forearm. Occlusion cuffs were placed at
the wrist and upper arm. After inflation of the distal cuff to exclude
hand blood flow, three to five flow measurements were made over a 1- to
2-min period at a proximal cuff pressure of 40 mmHg. Blood flow was
estimated from the rate of increase on forearm volume during venous
occlusion. These measurements were then averaged and divided by mean
blood pressure (Suntech), recorded simultaneously with flow, to
calculate forearm vascular resistance at rest and at each level of
LBNP.
For measurements in the brain, we used transcranial Doppler to measure
blood flow velocity in the middle cerebral artery (MCA) (1). This
technique allows noninvasive and repeatable measurements of blood flow
velocity on a beat-to-beat basis. A 2-MHz probe (Pioneer, Nicolet) was
placed over the temporal window and fixed at a constant angle and
position to obtain signals from the MCA according to standard
techniques (2). The reproducibility of velocity measurements during
LBNP was assessed in a separate group of four healthy subjects (aged 33 ± 7 yr) at time intervals ranging from 2 mo to 1 yr. No significant
change in percent decreases of velocity (measurements of velocity at
each level of LBNP divided by baseline value) during maximal LBNP was
observed between the repeated tests, confirming the reproducibility of
this response.
The finger pressure and MCA-velocity signals were sampled at 1 kHz and
digitized at 12 bits (Metrabyte, DAS-20) with use of a personal
computer. Real-time beat-to-beat mean values of pressure and velocity
were generated and displayed by using custom data-acquisition software.
Mean pressure and velocity averaged over the last minute of each level
of LBNP were considered as steady-state values for statistical
comparison. For the last six subjects studied, continuous beat-to-beat
mean velocity was obtained during a 6-min control period and for 3 min
at each level of LBNP and recorded along with beat-to-beat mean
pressure for off-line coherence analysis. This capability was not
available during the experiments in the first six subjects, and
therefore the data are only available for
n = 6.
Gosling pulsatility (systolic diastolic/mean velocity) was used
as an index of vascular resistance. This ratio describes the shape of
the CBF velocity waveforms. It represents the proportion of flow energy
that is pulsatile and is related to the elasticity of the vascular
system; changes in pulsatility reflect changes in cerebral small-vessel
resistance (31). Because pulsatility of the velocity waveform is
affected importantly by systemic pulse pressure, we corrected for this
effect by dividing the velocity pulsatility by arterial pressure
pulsatility to derive a corrected pulsatility ratio (19).
Coherence analysis.
The correlation between the beat-to-beat changes in arterial pressure
and CBF velocity was evaluated by the magnitude-squared coherence
function (MSC), defined as
|
|
RESULTS
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
50 mmHg LBNP
(Fig. 2A). At maximal
LBNP, it fell significantly at the point of presyncope. In contrast,
mean CBF velocity decreased significantly by 14, 20, and 45% at
40 mmHg, 50 mmHg, and maximal LBNP
(P < 0.05), respectively (Fig.
2B). Simultaneously, the
corrected pulsatility ratio increased significantly at 40
mmHg and maximal LBNP (P < 0.05),
suggestive of downstream cerebral vasoconstriction (Fig.
2C).
, Pre-bed rest; 
,
post-bed rest. * P < 0.05 compared with rest.
After bed rest, mean arterial pressure decreased significantly at
50 mmHg and maximal LBNP (P < 0.05) (Fig. 2A). Mean CBF velocity
fell at lower levels of LBNP compared with pre-bed rest, with
significant decreases from baseline by 16% at 30 mmHg and 21, 35, and 39% at 40 mmHg, 50 mmHg, and maximal LBNP,
respectively (P < 0.05) (Fig.
2B). Similar to pre-bed rest, the
corrected pulsatility ratio increased significantly at 50 mmHg
and maximum LBNP (P < 0.05) (Fig.
2C). Compared with pre-bed rest,
there was no significant change between the baseline velocity
measurements. However, mean velocity was less by 11, 10, and 21% at
30 mmHg, 40 mmHg, and 50 mmHg LBNP, respectively,
after compared with before bed rest (P < 0.05).
Coherence analysis.
Representative time series (Fig. 3,
A and
C) and power spectra (Fig. 3,
B and
D) of beat-to-beat changes in mean
arterial pressure and CBF velocity from one subject at rest are shown
in Fig. 3. Similar to the changes in arterial pressure,
variation of velocity showed a range of 29% change around the mean
value and a complex pattern with prominent low-frequency components (Fig. 3, C and
D). Typical coherence functions
estimated from the beat-to-beat changes in pressure and velocity are
shown in Fig. 4 at rest and during LBNP.
There was an obvious peak in the low-frequency band (0.05~0.15 Hz) at
rest, and the low-frequency coherence indexes increased during LBNP
with the peak value approaching one at 40 and 50 mmHg
LBNP, suggesting that cerebral autoregulation in the low-frequency
range was impaired during high-level LBNP. There was no significant
change in the high-frequency coherence index during LNBP. After
bed rest, there was a trend for an increase in the
low-frequency coherence index at baseline, with a similar augmentation
during LBNP as observed before bed rest (Figs. 4 and
5). For all subjects, the low-frequency
coherence index increased by 61 and 66% at 40 and 50
mmHg LBNP before bed rest, respectively (P < 0.05) (Fig. 5). After bed rest,
the low-frequency coherence index increased earlier by 33% at
30 mmHg LBNP (P < 0.05) (Fig. 5) and 45 and 50% at 40 and 50 mmHg LBNP, respectively
(Fig. 5). However, because of subject dropout at higher levels of LBNP after bed rest, the increase in the low-frequency coherence index could
not be demonstrated statistically at high levels of LBNP.
40 and 50 mmHg,
n = 2. Symbols are defined as in Fig. 2. * P < 0.05 compared with
rest.
DISCUSSION
The primary new finding of the present study is that mean CBF velocity decreased earlier at lower levels of LBNP in the absence of changes in arterial pressure, and the magnitude of the decrease was greater after 2 wk of head-down-tilt bed rest, associated with a substantial reduction in orthostatic tolerance. Furthermore, the coherence between changes in pressure and velocity increased significantly during LBNP, and these increases occurred at lower levels of LBNP after bed rest. These results suggest an impairment of cerebral autoregulation after bed rest and may contribute to the reduced orthostatic tolerance.
Methodological considerations. In the present study, we used transcranial Doppler to measure flow velocity in the MCA to estimate changes in CBF (1, 2). It is important to emphasize that velocity is not necessarily equal to flow. Changes in velocity are proportional to changes in flow only if the diameter of the MCA is maintained constant (19). Because of the anatomic location of the MCA and technical limitations, measurement of MCA diameter in humans may be difficult. Despite this difficulty, both angiographic studies (15) and direct visualization of the MCA during surgery (13) have suggested that, during a variety of stimuli known to affect CBF, the diameter of the MCA changes minimally (<3.0%). Thus it is likely that changes in velocity measured by Doppler are proportional to changes in flow (19). To investigate the dynamic properties of cerebral autoregulation, we took the advantage of coherence analysis to quantify the dependence of changes in velocity on the changes in arterial pressure (12). Coherence analysis is a frequency-domain measurement of correlation between two signals (22). Therefore, a high coherence suggests a high correlation between the changes in velocity and pressure and may represent ineffective autoregulation (12). Alternatively, a low coherence suggests a poor correlation between changes in velocity and pressure and may represent effective autoregulation. However, coherence estimation may be degraded by extraneous noise presented in the measurements (22). In the present study, the estimation was based on beat-to-beat changes in mean arterial pressure and velocity, and the random measurement noise was therefore likely to be reduced by this averaging process. Moreover, the high coherence values estimated during LBNP suggest that the noise level in such recordings was relatively low. In the present study we assumed that relative changes in cerebral perfusion pressure would be reflected by the relative changes in mean arterial pressure in subjects in the supine position. We measured arterial pressure in the finger by using the method of photoplethysmography. The reliability of this method for arterial pressure measurement has been proved in both the time and frequency domain (24). Considering that the arterial pressure wave moves at a velocity of ~5-8 m/s in large vessels (23), we find that the time delay between the finger arterial pressure and cerebral arterial pressure should be small and negligible. Furthermore, although waveforms of arterial pressure differ in different vascular beds due to reflection of waves, mean arterial pressure measured in the finger is likely to be proportional to the mean pressure measured in the MCA (23). If we also assume that intracranial pressure is low and relatively constant in healthy subjects, changes in the mean finger arterial pressure should therefore represent the changes in the cerebral perfusion pressure. Bed-rest effects on CBF velocity. Spaceflight or ground-based simulations such as HDT bed rest remove or minimize hydrostatic gradients and cause a cephalad fluid shift (5, 30). These changes not only induce acute and adaptive hemodynamic responses by the systemic circulation, they also influence cerebral perfusion pressure and CBF (30). With acute exposure to HDT bed rest, cerebral blood velocity appears to increase with an increased intracranial arterial pressure (10, 17). However, after hours to days, velocity is indistinguishable from preflight measurements (3). When cerebral hemodynamics are assessed by a "resistance index," one study has shown a decrease in resistance during LBNP, and this change appeared not to be influenced by HDT bed rest (28). The authors argued that reduction in resistance may indicate efficient autoregulation to maintain blood flow during orthostatic stress. However, there are numerous problems with estimating resistance from an indirect index. Like other pulsatility indexes estimated from the velocity waveform, the resistance index (systolic diastolic/systolic
velocity) is importantly influenced by the systemic pressure
pulsatility. A preponderance of the evidence suggests that CBF velocity
decreases during orthostatic stress and is associated with cerebral
vasoconstriction and an increase in vascular resistance (6, 14, 19).
In the present study, we observed no significant change in mean
velocity at low levels of LBNP. However, with high levels of LBNP, mean
velocity decreased and the corrected pulsatility ratio increased
significantly without a significant change of mean arterial pressure.
These results further confirmed previous findings from this laboratory
and findings by others (6, 19). The present study extends
these previous observations by demonstrating that velocity fell earlier
at lower levels of LBNP and that the decrease was greater after 2 wk of
bed rest associated with a substantial reduction in orthostatic
tolerance. In a previous study (19), we demonstrated that, in subjects
who were prone to syncope during LBNP, the decease of velocity also
occurred earlier at lower levels of LBNP compared with more resistant
subjects. These changes occurred simultaneously with augmented
sympathetic activity, as manifested by a significant increase in heart
rate and both systemic and forearm vascular resistance. In a similar comparison involving the present study, in subjects after bed rest we
observed a greater fall in stroke volume and greater increase in
systemic and forearm vascular resistance during LBNP compared with
before bed rest (Table 1). Therefore, we speculate that sympathetic
activation may be more potentiated during orthostatic stress after bed
rest. Although the augmented sympathetic activity is crucial for
maintaining systemic blood pressure, it may eventually lead to cerebral
vasoconstriction and a decrease in CBF velocity, and, presumably, flow.
This outcome, although not likely to be a principal cause of syncope
during orthostatic stress in the absence of systemic hypotension (19,
21), may predispose subjects to hypotension-induced syncope and
partially contribute to the reduced orthostatic tolerance after bed
rest.
Bed-rest effects on dynamic autoregulation.
We previously hypothesized that, if the cerebral autoregulatory curve
shifts rightward during high levels of LBNP due to increased sympathetic activity, the operating point of perfusion pressure and
flow may fall below the lower limit range of the autoregulatory curve
even without a significant change in mean arterial pressure (19). In
this situation, changes in CBF velocity, and, presumably, flow, may
become more dependent on the changes in pressure and the coherence
between these two variables should be increased. In this study, the
low-frequency coherence indexes (0.05-0.15 Hz) increased significantly
at high levels of LBNP before bed rest and occurred earlier at
30 mmHg LBNP after bed rest. These changes may indicate an
impairment of dynamic autoregulation during orthostatic stress.
In summary, we have demonstrated a more prominent decrease in CBF
velocity during orthostatic stress after 2 wk of HDT bed rest,
associated with a substantial reduction in orthostatic tolerance. These
changes occurred simultaneously with a significant increase in
coherence between beat-to-beat mean arterial pressure and CBF velocity,
which suggests an impairment of cerebral autoregulation. Consequently,
this impairment of autoregulation may contribute to the reduced
orthostatic tolerance after adaptation to simulated microgravity.
ACKNOWLEDGEMENTS
We thank Dr. Cole A. Giller for comments and constructive discussion on this study and Kay Hood and Joyce Young for secretarial assistance.
FOOTNOTES
Address for reprint requests: B. D. Levine, Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Ave., Dallas, TX 75231 (E-mail: Levineb{at}wpmail.phscare.org).
Received 28 April 1997; accepted in final form 15 August 1997.
REFERENCES
| 1. | Aaslid, R., T. M. Marwalder, and H. Nornes. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J. Neurosurg. 57: 769-774, 1982[Medline]. |
| 2. |
American Academy of Neurology, Therapeutics, and Technology Assessment Subcommittee.
Assessment: transcranial Doppler ultrasound.
Neurology
40:
680-681,
1990 |
| 3. | Bagian, J. P., and P. Hackett. Cerebral blood flow: comparison of ground-based and spaceflight data and correlation with space adaptation syndrome. J. Clin. Pharmacol. 31: 1036-1040, 1991[Medline]. |
| 4. | Blomqvist, C. G. Orthostatic hypotension. In: Cardiology, edited by W. W. Parmley, and K. Chaterjee. Philadelphia, PA: Lippincott, 1990, p. 1-20. |
| 5. | Blomqvist, C. G., and H. L. Stone. Cardiovascular adjustments to gravitational stress. In: Handbook of Physiology. The Cardiovascular System. Bethesda, MD: Am. Physiol. Soc., 1983, sect. 2, vol. III, pt. 2, chapt. 28, p. 1025-1063. |
| 6. |
Bondar, R. L.,
M. S. Kassam,
F. Stein,
P. T. Dunphy,
S. Fortney,
and
M. L. Riedesel.
Simultaneous cerebrovascular and cardiovascular responses during presyncope.
Stroke
26:
1794-1800,
1995 |
| 7. |
Buckey, J. C.,
L. D. Lane,
B. D. Levine,
D. E. Watenpaugh,
S. J. Wright,
W. E. Moore,
F. A. Gaffney,
and
C. G. Blomqvist.
Orthostatic intolerance following spaceflight.
J. Appl. Physiol.
81:
7-18,
1996 |
| 8. | Carter, G. C., C. H. Knapp, and A. H. Nuttall. Estimation of the magnitude-squared coherence function via overlapped fast Fourier transform processing. IEEE Trans. Audio Electroacoustics 21: 337-344, 1973. |
| 9. |
Convertino, V. A.,
D. F. Doerr,
D. L. Eckberg,
J. M. Fritsch,
and
J. Vernikos-Danellis.
Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension.
J. Appl. Physiol.
68:
1458-1464,
1990 |
| 10. |
Frey, M. A. B.,
T. H. Mader,
J. P. Bagian,
J. B. Charles,
and
R. T. Meehan.
Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt.
J. Appl. Physiol.
74:
319-325,
1993 |
| 11. |
Fritsch, J. M.,
J. B. Charles,
B. S. Bennett,
M. M. Jones,
and
D. L. Eckberg.
Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses.
J. Appl. Physiol.
73:
664-671,
1992 |
| 12. | Giller, C. A. The frequency dependent behavior of cerebral autoregulation. Neurosurgery 27: 362-367, 1990[Medline]. |
| 13. | Giller, C. A., G. Bowman, H. Dyer, and L. Mootz. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery 32: 737-741, 1993[Medline]. |
| 14. |
Grubb, B. P.,
G. Gerard,
K. Roush,
P. Temesy-Armos,
P. Montford,
L. Elliot,
H. Hahn,
and
P. Brewster.
Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope: a paradoxic and unexpected response.
Circulation
84:
1157-1163,
1991 |
| 15. | Huber, P., and J. Handa. Effect of contrast material, hypercapnia, hyperventilation, hypertonic glucose and papaverine on the diameter of the cerebral arteries. Invest. Radiol. 2: 17-32, 1967[Medline]. |
| 16. |
Kallay, M. C.,
R. W. Hyde,
R. J. Smith,
R. L. Rothbard,
and
B. F. Schreiner.
Cardiac output by rebreathing in patients with cardiopulmonary diseases.
J. Appl. Physiol.
63:
201-210,
1987 |
| 17. |
Kawai, Y.,
G. Murthy,
D. E. Watenpaugh,
G. A. Breit,
C. W. Deroshia,
and
A. R. Hargens.
Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt.
J. Appl. Physiol.
74:
3046-3051,
1993 |
| 18. |
Levine, B. D.,
J. C. Buckey,
J. M. Fritsch,
C. W. Yancy,
D. E. Watenpaugh,
D. L. Eckberg,
and
C. G. Blomqvist.
Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance.
J. Appl. Physiol.
70:
112-122,
1991 |
| 19. |
Levine, B. D.,
C. A. Giller,
L. D. Lane,
J. C. Buckey,
and
C. G. Blomqvist.
Cerebral versus systemic hemodynamics during graded orthostatic stress in humans.
Circulation
90:
298-305,
1994 |
| 20. |
Levine, B. D.,
L. D. Lane,
J. C. Buckey,
D. B. Friedman,
and
C. G. Blomqvist.
Ventricular pressure-volume and Frank-Starling relations in endurance athletes: implications for orthostatic tolerance and exercise performance.
Circulation
84:
1016-1023,
1991 |
| 21. |
Levine, B. D.,
J. H. Zuckerman,
and
J. A. Pawelczyk.
Cardiac atrophy after bedrest deconditioning: a non-neural mechanism for orthostatic intolerance.
Circulation.
96:
517-525,
1997 |
| 22. | Marmarelis, V. Z. Coherence and apparent transfer function measurements for nonlinear physiological systems. Ann. Biomed. Eng. 16: 143-157, 1988[Medline]. |
| 23. | Nichols, W. W., and M. F. O'Rourke. McDonald's blood flow in arteries: theoretical, experimental and clinical principles. Philadelphia, PA: Lea and Febiger, 1990, p. 77-250. |
| 24. |
Omboni, S.,
G. Parati,
A. Frattola,
E. Mutti,
M. D. Rienzo,
P. Castiglioni,
and
G. Mancia.
Spectral and sequence analysis of finger blood pressure variability: comparison with analysis of intra-arterial recordings.
Hypertension
22:
26-33,
1993 |
| 25. |
Parati, G.,
J. P. Saul,
M. D. Rienzo,
and
G. Mancia.
Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation: a critical appraisal.
Hypertension
25:
1276-1286,
1995 |
| 26. | Paulson, O. B., S. Strandgaard, and L. Edvinsson. Cerebral autoregulation. Cerebrovasc. Brain. Metab. Rev. 2: 161-192, 1990[Medline]. |
| 27. | Pawelczyk, J. A., B. D. Levine, G. K. Prisk, B. F. Shykoff, A. R. Elliot, and E. Rosow. Accuracy and precision of flight systems for determination of cardiac output by soluble gas rebreathing. In: Proceedings of the 1995 NASA/AAIA Life Sciences and Space Medicine Conference October 1995. Houston, TX: NASA/AAIA, 1995, XII, p. LS95 - LS130. |
| 28. | Traon, A. P., P. Vasseur, P. Arbeille, A. Guell, A. Bes, and C. Gharib. Effects of 28-day head-down tilt with and without countermeasures on Lower body negative pressure responses. Aviat. Space Environ. Med. 66: 982-991, 1995[Medline]. |
| 29. | Triebwasser, J. H., R. L. Johnson, R. P. Burpo, J. C. Campbell, W. C. Reardon, and C. G. Blomqvist. Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements. Aviat. Space Environ. Med. 48: 203-209, 1977[Medline]. |
| 30. | Watenpaugh, D. E., and A. R. Hargens. The cardiovascular system in microgravity. In: Handbook of Physiology. Environmental Physiology. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 4, vol. I, chapt. 29, p. 631-674. |
| 31. | Woodcock, J. P., R. G. Gosling, and D. E. Fitzgerald. A new non-invasive technique for assessment of superficial femoral artery obstruction. Br. J. Surg. 59: 226-231, 1972[Medline]. |
This article has been cited by other articles:
|
|
 |
|
  D. E. Watenpaugh, D. D. O'Leary, S. M. Schneider, S. M. C. Lee, B. R. Macias, K. Tanaka, R. L. Hughson, and A. R. Hargens Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance J Appl Physiol, December 1, 2007; 103(6): 1964 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Iwasaki, B. D. Levine, R. Zhang, J. H. Zuckerman, J. A. Pawelczyk, A. Diedrich, A. C. Ertl, J. F. Cox, W. H. Cooke, C. A. Giller, et al. Human cerebral autoregulation before, during and after spaceflight J. Physiol., March 15, 2007; 579(3): 799 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Carter III, S. N. Cheuvront, C. R. Vernieuw, and M. N. Sawka Hypohydration and prior heat stress exacerbates decreases in cerebral blood flow velocity during standing J Appl Physiol, December 1, 2006; 101(6): 1744 - 1750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Prisby, M. K. Wilkerson, E. M. Sokoya, R. M. Bryan Jr., E. Wilson, and M. D. Delp Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms J Appl Physiol, July 1, 2006; 101(1): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Serrador, R. L. Hughson, J. M. Kowalchuk, R. L. Bondar, and A. W. Gelb Cerebral blood flow during orthostasis: role of arterial CO2 Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1087 - R1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cui, S. Durand, B. D. Levine, and C. G. Crandall Effect of skin surface cooling on central venous pressure during orthostatic challenge Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2429 - H2433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Guo, F. Schaller, N. Tierney, S. A. Smith, and X. Shi New Insight into the Mechanism of Cardiovascular Dysfunction in the Elderly: Transfer Function Analysis Experimental Biology and Medicine, September 1, 2005; 230(8): 549 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schondorf, J. Benoit, and R. Stein Cerebral autoregulation is preserved in postural tachycardia syndrome J Appl Physiol, September 1, 2005; 99(3): 828 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogoh, P. J. Fadel, R. Zhang, C. Selmer, O. Jans, N. H. Secher, and P. B. Raven Middle cerebral artery flow velocity and pulse pressure during dynamic exercise in humans Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1526 - H1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Wilkerson, L. A. Lesniewski, E. M. Golding, R. M. Bryan Jr., A. Amin, E. Wilson, and M. D. Delp Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1652 - H1661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogoh, M. K. Dalsgaard, C. C. Yoshiga, E. A. Dawson, D. M. Keller, P. B. Raven, and N. H. Secher Dynamic cerebral autoregulation during exhaustive exercise in humans Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1461 - H1467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Howden, J. T. Lightfoot, S. J. Brown, and I. L. Swaine The effects of breathing 5% CO2 on human cardiovascular responses and tolerance to orthostatic stress Exp Physiol, July 1, 2004; 89(4): 465 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Durand, J. Cui, K. D. Williams, and C. G. Crandall Skin surface cooling improves orthostatic tolerance in normothermic individuals Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R199 - R205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Cui, R. Zhang, T. E. Wilson, S. Witkowski, C. G. Crandall, and B. D. Levine Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2105 - H2110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ma, C. I. Kahwaji, Z. Ni, N. D. Vaziri, and R. E. Purdy Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content J Appl Physiol, January 1, 2003; 94(1): 83 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Wilson, J. Cui, R. Zhang, S. Witkowski, and C. G. Crandall Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance during tilting in heated humans J Appl Physiol, July 1, 2002; 93(1): 85 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chouker, L. Smith, F. Christ, I. Larina, I. Nichiporuk, V. Baranov, E. Bobrovnik, L. Pastushkova, K. Messmer, K. Peter, et al. Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men J Appl Physiol, April 1, 2002; 92(4): 1619 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Wilkerson, P. N. Colleran, and M. D. Delp Acute and chronic head-down tail suspension diminishes cerebral perfusion in rats Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H328 - H334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-F. Zhang Vascular adaptation to microgravity: what have we learned? J Appl Physiol, December 1, 2001; 91(6): 2415 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Serrador, S. J. Wood, P. A. Picot, F. Stein, M. S. Kassam, R. L. Bondar, A. H. Rupert, and T. T. Schlegel Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation J Appl Physiol, November 1, 2001; 91(5): 1986 - 1994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-N. Zhang, L.-F. Zhang, and J. Ma Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery J Appl Physiol, June 1, 2001; 90(6): 2296 - 2305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
6
