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Medical Sciences Division, National Aeronautics and Space Administration Johnson Space Center, and KRUG Life Sciences, Houston, Texas 77058; and Centre for Advanced Technology Education, Ryerson Polytechnic University, Toronto, Ontario, Canada M5B 2K3
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Fritsch-Yelle, Janice M., Peggy A. Whitson, Roberta L. Bondar, and Troy E. Brown. Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight.
J. Appl. Physiol. 81(5):
2134-2141, 1996.
Postflight orthostatic intolerance is
experienced by virtually all astronauts but differs greatly in degree
of severity. We studied cardiovascular responses to upright posture in
40 astronauts before and after spaceflights lasting up to 16 days. We
separated individuals according to their ability to remain standing
without assistance for 10 min on landing day. Astronauts who could not
remain standing on landing day had significantly smaller increases in
plasma norepinephrine levels with standing than did those who could
remain standing (105 ± 41 vs. 340 ± 62 pg/ml;
P = 0.05). In addition, they had
significantly lower standing peripheral vascular resistance (23 ± 3 vs. 34 ± 3 mmHg · l
1 · min;
P = 0.02) and greater decreases in
systolic (
28 ± 4 vs. 11 ± 3 mmHg;
P = 0.002) and diastolic (14 ± 7 vs. 3 ± 2 mmHg; P = 0.0003) pressures. The presyncopal group also had
significantly lower supine (16 ± 1 vs. 21 ± 2 mmHg · l1 · min;
P = 0.04) and standing (23 ± 2 vs.
32 ± 2 mmHg · l1 · min;
P = 0.038) vascular resistance, supine
(66 ± 2 vs. 73 ± 2 mmHg; P = 0.008) and standing (69 ± 4 vs. 77 ± 2 mmHg;
P = 0.007) diastolic pressure, and
supine (109 ± 3 vs. 114 ± 2 mmHg; P = 0.05) and standing
(99 ± 4 vs. 108 ± 3 mmHg; P = 0.006) systolic pressures before flight. This is the first study to
clearly document these differences among presyncopal and nonpresyncopal
astronauts after spaceflight and also offer the possibility of
preflight prediction of postflight susceptibility. These results
clearly point to hypoadrenergic responsiveness, possibly centrally
mediated, as a contributing factor in postflight orthostatic
intolerance. They may provide insights into autonomic dysfunction in
Earthbound patients.
orthostatic hypotension; adrenergic
INTRODUCTION VIRTUALLY EVERY ASTRONAUT returning from space suffers
some degree of orthostatic intolerance. Returning astronauts exhibit signs and symptoms when subjected to upright posture that are similar
to those in patients with orthostatic intolerance due to autonomic
dysfunction. These include nausea, vomiting, lightheadedness (presyncope), and fainting (syncope) (4). However, orthostatic hypotension in returning astronauts is spontaneously reversible, resolving without treatment in several days (10, 12, 30). The etiology
of orthostatic intolerance after spaceflight is not yet understood. The
known losses of plasma volume after spaceflight (19) have been thought
to contribute to the problem. However, in head-down bed rest studies
[commonly employed on Earth to mimic the fluid changes associated
with spaceflight (20)], restoration of plasma volume does not
restore orthostatic tolerance (3). We have previously shown that a
reduction in arterial baroreflex function after spaceflight is related
to orthostatic intolerance (10, 12).
There is a wide range of individual susceptibility to orthostatic
intolerance after spaceflight. Some individuals have severe symptoms,
whereas others are less affected. These differences have not been
explored. No preflight predictor of postflight orthostatic intolerance
has been previously identified, nor have physiological differences
between individuals who do and who do not experience severe symptoms
(presyncope or syncope) on landing day been previously reported. The
purpose of this study was to characterize differences in physiological
responses of astronauts who are and who are not susceptible to
orthostatic hypotension after spaceflight. We studied hemodynamic and
neuroendocrine responses to orthostatic stress in 40 astronauts (8 women and 32 men), whose mean age was 40 ± 1 yr, before and after
shuttle missions lasting 8-16 days. Analyses and discussion in
this study focus not on preflight to postflight changes, which have
been reported previously (4, 10, 12, 30), but rather on differences
between those astronauts who did and those who did not become
presyncopal on landing day.
METHODS This protocol was approved by the Johnson Space Center Human Research
Policy and Procedures Committee. Studies were conducted 30 and 10 days
before launch, on landing day (1-2 h after landing), and 3 days
after landing. On each test day, subjects had abstained from caffeine,
alcohol, and any medications for the preceding 12 h; were at least 2 h
postprandial; and had not exercised heavily in 24 h. Subjects were
instrumented for electrocardiogram, manual blood pressure
(sphygmomanometer), beat-to-beat blood pressure (Finapres, Ohmeda,
Inglewood, CO), and transcranial Doppler (Medasonics, Fremont, CA). An
intravenous catheter was inserted into an antecubital vein. After a
20-min supine rest period, plasma volume was determined by using carbon
monoxide rebreathing (6, 25, 28). A blood sample was drawn for
norepinephrine, epinephrine, and plasma renin activity. Then
two-dimensional and M-mode echocardiography were used to determine
aortic cross-sectional diameter, and aortic flow was measured with
continuous-wave Doppler ultrasound. Middle cerebral artery flow
velocity was measured through the right or left temporal window with
2-MHz pulsed transcranial Doppler ultrasound (1). Measurements
continued while the subjects remained supine for 5 additional min.
Subjects were then assisted to a standing position by three
investigators. Subjects were lifted by being grasped behind both
shoulders while their feet were swept off the bed to minimize
artifactual blood pressure changes with the effort of standing. The
finger with the continuous arterial pressure device was held at heart
level by a system of Velcro straps. Subjects remained standing without
support for 10 min. A final blood sample was drawn at the end of the
standing period. Subjects who became presyncopal were returned to a
supine position, and blood samples were drawn immediately. All data
were recorded on digital tape for later analyses. All analog signals
were also recorded on paper.
On landing day, all subjects consumed the equivalent of at least 8 g of
NaCl and 1 liter of water 1-2 h before landing (the standard
fluid-loading procedure). Between landing and the time of the data
collection, they drank an average of 556 ± 121 ml water (ranging
from 0 to 1,895 ml).
RESULTS
Mean data for the last minute supine and last minute standing on landing day for all subjects are shown in Table 1. Also shown are the supine-to-standing differences for each variable. The most striking and fundamental intergroup difference was the significantly lower norepinephrine response in the presyncopal group, who had only one-third as great an increase with standing as did the nonpresyncopal group (P = 0.05). There was a significant group effect for peripheral vascular resistance (P = 0.005), and standing vascular resistance was one-third lower in the presyncopal group (P = 0.035). There was a significant group effect for diastolic pressure (P = 0.0001). In fact, diastolic pressure fell precipitously on standing in presyncopal subjects but actually increased slightly in nonpresyncopal subjects (P = 0.0003). There were significant group (P = 0.001) and day (P = 0.025) effects for systolic pressure. Both supine and standing systolic pressures were lower in the presyncopal group (P = 0.03 and P = 0.00005, respectively). There were significant group (P = 0.002) and day (P = 0.0001) effects for heart rate. Heart rate was higher both supine and standing in the presyncopal group (P = 0.028 and P = 0.0078, respectively). Cerebral vascular resistance in the middle cerebral artery was lower standing in the presyncopal group (P = 0.011). There were no intergroup differences in stroke volume, cardiac output, plasma renin activity, or middle cerebral artery mean flow velocity. Stroke volume showed a significant day effect (P = 0.0001). Plasma epinephrine showed significant day (P = 0.004) and day × group (P = 0.02) effects.
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1 · min
(P = 0.82) for the nonpresyncopal
group and 21.2 ± 1.4 vs. 23.3 ± 1.7 mmHg · l1 · min
(P = 0.59) for the
presyncopal group] or postflight [30.5 ± 2.1 vs. 33.8 ± 2.7 mmHg · l1 · min
(P = 0.79) for the nonpresyncopal
group and 23.1 ± 3.8 vs. 21.5 ± 3.5 mmHg · l1 · min
(P = 0.18) for the entire presyncopal
group].
Plasma volumes for both groups are shown in Tables 1, 2, and 3. No significant intergroup differences were found either before or after flight.
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0.9 ± 3.1 vs. 1.6 ± 1.8 mmHg · l1 · min;
not significant between groups; Fig.
3B). The presyncopal group had a
greater loss in standing diastolic (16 ± 7 vs. 1 ± 2 mmHg; P = 0.003, between
groups; Fig. 3C) and systolic
(17 ± 4 vs. 5 ± 2 mmHg;
P = 0.028 between groups; Fig.
3D) pressures after spaceflight and
a greater increase in heart rate with standing (23 ± 4 vs. 13 ± 2 beats/min; P = 0.023 between groups; Fig. 3E). The
differences in responses to standing between preflight and 3 days after
landing are presented in Fig. 4. Similar to
what is presented in Table 3, the intergroup differences seen several days after landing have mostly returned to preflight status. There were
no intergroup differences between responses preflight and 3 days after
landing.
0.05 between groups.
P 0.01 between groups.
DISCUSSION
This study provides three insights into orthostatic hypotension after spaceflight. First, individuals have measurable differences in susceptibility to postspaceflight orthostatic hypotension. Second, presyncope on landing day is at least partially attributable to hypoadrenergic responses during upright posture. Third, there may be a preflight predisposition in the susceptible individuals. These findings not only suggest mechanisms of orthostatic tolerance following spaceflight but may also have clinical relevance. We describe reversible autonomic dysfunction that resolves without treatment within a few days. These results may have relevance to irreversible autonomic function in Earthbound patients.
Hypoadrenergic responses on landing day. Subnormal increases in norepinephrine with upright posture indicate a functional change in the neurogenic feedback loop, which includes arterial baroreceptors, brainstem, spinal tracts, and sympathetic nerves. Normal supine, but subnormal standing, plasma norepinephrine levels are seen in patients with impaired central modulation of baroreceptor input, such as diabetes (33), cervical spinal cord transection (33), and the Shy-Drager syndrome (26, 33). On the other hand, patients with peripheral neuropathy usually have subnormal supine and subnormal standing norepinephrine levels (33). These data therefore suggest that human cardiovascular adaptations to microgravity include changes in central modulation of baroreceptor inputs that cause a hypoadrenergic response to orthostasis that results in presyncope in 25% of returning astronauts. There are anecdotal data that have been reported before (12) that may indirectly support the idea of changes in central modulation of autonomic function. These are the various in-flight symptoms reported by astronauts during interviews. They include urinary retention and/or incontinence; diarrhea; constipation; changes in vision, taste, smell, thirst, and appetite; and hypesthesias and parasthesias in the feet. These symptoms have not been investigated, but they may be relevant to an understanding of in-flight autonomic changes. Differences between presyncopal and nonpresyncopal groups. These data not only suggest a mechanism for postflight orthostatic intolerance but also show clear differences between susceptible and nonsusceptible individuals and, for the first time, raise the possibility of predicting susceptible individuals before launch. The intergroup differences before flight suggest that there is a subset of the normal population who has orthostatic responses within normal ranges before flight but who is predisposed to postflight orthostatic intolerance. This group had norepinephrine responses to standing that were normal both before and 3 days after flight, but during every test session these subjects had lower vascular resistance and arterial pressures and higher heart rates than did those in the other group. This suggests possible preflight intergroup differences in venous compliance and /or vascular responsiveness. Spaceflight affects this group differentially. Whereas the nonsusceptible group had increased adrenergic responses to upright posture after flight, this group had a subnormal adrenergic response, which results in presyncope. Influence of gender on orthostatic tolerance. This laboratory has performed stand tests on 91 astronauts who flew on the shuttle but were not in this study (17 women and 74 men). Of those, six women (35%) and five men (7%) became presyncopal on landing day (J. M. Fritsch-Yelle, unpublished observations). The majority of the susceptible astronauts in the present study also were women. Although this is not a common finding in the literature, there are many documented gender differences in cardiovascular responses to stress. Women have higher resting heart rates than do men (14) and also respond to cardiovascular stress with greater heart rate increases (2, 9, 15-17), whereas men respond primarily with greater increases in vascular resistance (9, 15-17). Several lines of recent evidence suggest that premenopausal women may be limited in their capacity for vascular responsiveness. It has been suggested that women may have fewer or less sensitive peripheral adrenergic receptors (8) and lower sensitivity to adrenergic nerve stimulation than do men (22). Estrogen treatment has been shown to decrease blood pressure in spontaneously hypertensive rats (18). When stressed, female rats release less norepinephrine than do males (7). Many female-male differences in cardiovascular responses have been shown to be estrogen-related, mediated through endothelium-dependent relaxing factor (nitric oxide) (29, 31, 32). These indirect vasodilatory effects of estrogen may contribute to the smaller vasoconstrictive responsiveness in women compared with men during orthostatic stress. If women compensate with greater heart rate responses, it may leave them more susceptible than men to orthostatic hypotension in situations in which autonomic function is compromised, for example, after spaceflight. Importantly in the present study, the group that was destined to become presyncopal on landing day (primarily female) and the group who was not destined to become presyncopal on landing day (primarily male) showed the same preflight differences in cardiovascular responses as the female-male differences mentioned above. In addition to gender, another factor should at least be mentioned. Most of the nonpresyncopal group in this study were career pilots of high-performance aircraft before they became astronauts. All the pilots were men. These people would not have been successful in that career if they did not have a high tolerance to G forces (either learned or inherent). Cerebral autoregulation. The reductions in cerebral vascular resistance with standing we documented are consistent with the accepted concept of cerebral autoregulation (21). On landing day, the presyncopal group showed a greater compensatory decrease in cerebrovascular resistance (vasodilatation) in response to the greater fall in mean arterial pressure. However, this was not adequate to maintain mean flow velocity in the face of the collapse of systemic arterial pressure. Because both groups did not experience this calamitous fall in arterial pressure, no conclusions can be drawn about intergroup differences in cerebral autoregulation. Other cardiovascular changes associated with spaceflight. This is not the first report of in-flight changes in autonomic regulation of cardiovascular function that affect postflight function. We previously reported attenuation of the vagally mediated carotid baroreceptor cardiac reflex response that begins as early as the 2nd day in flight and persists for ~1 wk postflight (10-12). On landing day, reductions in this reflex correlate directly with lower standing systolic pressures. We have also reported in-flight decreases in heart rate and arterial pressure that are reversed on landing day and in-flight decreases in frequency of cardiac dysrhythmias (13). Immediately after shuttle landing, we have reported standing heart rates as high as 160 beats/min, as the cardiovascular system struggles to support arterial pressure, yet systolic pressure can fall as much as 25 mmHg. Unfortunately, no previous study has separated presyncopal and nonpresyncopal data for analyses. For example, although there are reports that in-flight catecholamines are low (C. L. Huntoon, personal communication) and in-flight arterial pressures and heart rates are low (13), it has never been determined whether in-flight measurements are different in those who become presyncopal on landing day. Presumably they are. If in-flight sympathetic activity/catecholamines in presyncopal astronauts is differentially low, for example, an upregulation of adrenergic receptors might be expected. If postsynaptic
1-adrenergic
receptors were upregulated, an increased resistance response would be
expected. If, however, presynaptic 2-receptors are upregulated in
this group, or central modulation is dysfunctional, norepinephrine
release and peripheral resistance would be inhibited as in the present
study. A previous study addressed this issue indirectly.
Whitson et al. (30) showed that, in subjects on standing, the ratio of
increase in total peripheral resistance to increase in norepinephrine
was reduced on landing day, indicating that
1-receptors probably were not
upregulated. However, presyncopal and nonpresyncopal subjects were not
separated in that study. These issues have not been resolved.
Role of differences in plasma volume.
These results do not support the notion that loss of plasma volume is a
primary cause of postflight orthostatic hypotension. These data support
previous findings from bed rest studies that showed that restoration of
plasma volumes did not restore post-bed rest orthostatic tolerance (3).
Limitations.
When subjects in this study became presyncopal before the end of 10 min
of standing, they were returned to the supine position for the final
blood draw. We were concerned that plasma norepinephrine levels in this
group may have been low partially as a result of their decreased time
in the upright posture. To address this concern, we repeated the stand
test protocol in the laboratory by using 11 normal volunteers (3 women,
8 men) who had not flown in space. We drew blood samples for
norepinephrine analysis after 2, 4, 6, 8, and 10 min of standing,
rather than only at the end. All subjects had passed the same Air Force
class III physical that the astronauts must pass. The volunteers' mean
age was 31 ± 2 yr. These subjects experienced both systolic and
diastolic pressure decreases of only 1 ± 1 mmHg during standing.
The changes in norepinephrine levels at 2, 4, 6, 8, and 10 min of
standing for these laboratory subjects were 48 ± 7, 60 ± 8, 178 ± 7, 205 ± 5, and 190 ± 6 pg/ml. When these
data were compared with landing day norepinephrine levels in
presyncopal astronauts, six of the eight presyncopal astronauts had
norepinephrine responses at the time of their presyncope that were
below those in the normal group after the same duration of standing.
Thus, even though they experienced tremendous arterial pressure falls
(Table 1), they still did not have norepinephrine responses as great as
those in normal subjects who had not been in space and were not
experiencing arterial pressure declines.
In summary, we studied the integrated responses to standing in
astronauts before and after spaceflight. We found that there are some
who are more susceptible to orthostatic intolerance immediately after
spaceflight (characterized by hypoadrenergic responses to upright
posture), who recover spontaneously within a few days, and who show a
preflight predisposition to this susceptibility. These findings may
have significance for Earthbound patients with orthostatic hypotension
as well as for space travelers.
ACKNOWLEDGEMENTS
We are indebted to the astronauts who participated in this study. We also thank the personnel in the Cardiovascular and Biochemistry Laboratories at Johnson Space Center and the Laboratory at the Centre for Advanced Technology Education at Ryerson Polytechnic University in Toronto for their tireless efforts in accomplishing this project. We also thank Michael G. Ziegler for his contribution of the enzymes for the catecholamine analyses and critical review of the manuscript and Urs A. Leuenberger for assistance in echocardiography on landing days.
FOOTNOTES
Address for reprint requests: J. M. Fritsch-Yelle, Cardiovascular Laboratory, SD3/, Johnson Space Center, Houston, TX 77058.
Received 24 January 1996; accepted in final form 21 July 1996.
REFERENCES
| 1. | Aaslid, R., T. Markwalder, and S. Nornes. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J. Neurosurg. 57: 769-774, 1982. |
| 2. | Abdel-Rahman, A. R. A., R. H. Merrill, and W. R. Wooles. Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans. J. Appl. Physiol. 77: 606-613, 1994. |
| 3. | Blomqvist, C. G., J. V. Nixon, R. L. Johnson, Jr., and J. H. Mitchell. Early cardiovascular adaptation to zero gravity simulated by head-down tilt. Acta Astronaut. 7: 543-553, 1980. |
| 4. | Bungo, M. W., and P. C. Johnson, Jr. Cardiovascular examinations and observations of deconditioning during the space shuttle orbital flight test program. Aviat. Space Environ. Med. 54: 1001-1004, 1983. |
| 5. | Da Prada, M., and G. Zurcher. Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 19: 1161-1174, 1976. |
| 6. | Dahms, T. E., and S. M. Horvath. Rapid, accurate technique for determination of carbon monoxide in blood. Clin. Chem. 20: 533-537, 1974. |
| 7. | Du, X.-J., R. A. Riemersma, and A. M. Dart. Cardiovascular protection by oestrogen is partly mediated through modulation of autonomic nervous function. Cardiovasc. Res. 30: 161-165, 1995. |
| 8. | Freedman, R. R., S. C. Sabharwal, and N. Desai. Sex differences in peripheral vascular adrenergic receptors. Circ. Res. 61: 581-585, 1987. |
| 9. | Frey, M. A. B., C. M. Tomaselli, and W. G. Hoffler. Cardiovascular responses to postural changes: differences with age for women and men. J. Clin. Pharmacol. 34: 394-402, 1994. |
| 10. | 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. |
| 11. | Fritsch, J. M., and D. L. Eckberg. Effects of weightlessness on human baroreflex function (Abstract). Aviat. Space Environ. Med. 63: 439, 1992. |
| 12. | Fritsch-Yelle, J. M., J. B. Charles, M. M. Jones, L. A. Beightol, and D. L. Eckberg. Spaceflight alters autonomic regulation of arterial pressure in humans. J. Appl. Physiol. 77: 1776-1783, 1994. |
| 13. | Fritsch-Yelle, J. M., J. B. Charles, M. M. Jones, and M. L. Wood. Microgravity decreases heart rate and arterial pressure in humans. J. Appl. Physiol. 80: 910-914, 1996. |
| 14. | Gillum, R. F. The epidemiology of resting heart rate in a national sample of men and women: associations with hypertension, coronary heart disease, blood pressure, and other cardiovascular risk factors. Am. Heart J. 116: 163-174, 1988. |
| 15. | Girdler, S. S., and K. C. Light. Hemodynamic stress responses in men and women examined as a function of female menstrual cycle phase. Int. J. Psychophysiol. 17: 233-248, 1994. |
| 16. | Girdler, S. S., J. R. Turner, A. Sherwood, and K. C. Light. Gender differences in blood pressure control during a variety of behavioral stressors. Psychosom. Med. 52: 571-591, 1990. |
| 17. | Gotshall, R. W., P.-F. Tsai, and M. A. B. Frey. Gender-based differences in the cardiovascular response to standing. Aviat. Space Environ. Med. 62: 855-859, 1991. |
| 18. | Iams, S. G., and B. C. Wexler. Inhibition of the development of spontaneous hypertension in SH rats by gonadectomy or estradiol. J. Lab. Clin. Med. 94: 608-616, 1979. |
| 19. | Johnson, P. C., T. B. Driscoll, and A. D. LeBlanc. Blood volume changes. In: Biomedical Results from Skylab, edited by R. S. Johnston, and L. F. Dietlein. Washington, DC: NASA, 1977, p. 235-241. (NASA Spec. Rep. 377) |
| 20. | Kakurin, L. I., V. I. Lobachik, V. M. Mikhailov, and Y. A. Senkevich. Antiorthostatic hypokinesia as a method of weightlessness simulation. Aviat. Space Environ. Med. 47: 1083-1086, 1976. |
| 21. | Lassen, N. A. Autoregulation of cerebral blood flow. Circ. Res. 14: I-201-I-204, 1964. |
| 22. | Li, Z., and S. P. Duckles. Influence of gender on vascular reactivity in the rat. J. Pharmacol. Exp. Ther. 268: 1426-1431, 1994. |
| 23. | Lilliefors, H. W. On the Kolmogorov-Smirnov test for normality with mean and variance unknown. J. Am. Stat. Assoc. 62: 399-402, 1967. |
| 24. | Low, P. A. Laboratory evaluation of autonomic failure. In: Clinical Autonomic Disorders, Evaluation and Management, edited by P. A. Low. Boston, MA: Little, Brown, 1993, p. 169-195. |
| 25. | Maas, A. H. J., M. L. Hamelink, and J. M. DeLeeuw. An evaluation of the spectrophotometric determination of HbO2, HbCO and HB in blood with the CO-oximeter IL 182. Clin. Chem. Acta 29: 303-309, 1970. |
| 26. | Robertson, D., I. Biaggioni, R. Mosqueda-Garcia, and R. M. Robertson. Orthostatic hypotension of prolonged weightlessness: clinical models. Acta Astronaut. 27: 97-101, 1992. |
| 27. | Sealy, J. E., and J. H. Laragh. Radioimmunoassay of plasma renin activity. Semin. Nucl. Med. 5: 189-202, 1975. |
| 28. | Thomsen, J. K., N. Fogh-Andersen, K. Bülow, and A. Devantier. Blood and plasma volumes determined by carbon monoxide gas, 99mTc-labelled erythrocytes, 125I-albumin and the T 1824 technique. Scand. J. Clin. Lab. Invest. 51: 185-190, 1991. |
| 29. | Volterrani, M., G. Rosano, A. Coats, C. Beale, and P. Collins. Estrogen acutely increases peripheral blood flow in postmenopausal women. Am. J. Med. 99: 119-122, 1995. |
| 30. | Whitson, P. A., J. B. Charles, W. J. Williams, and N. M. Cintròn. Changes in sympathoadrenal response to standing in humans after spaceflight. J. Appl. Physiol. 79: 428-433, 1995. |
| 31. | Williams, J. K., M. R. Adams, D. M. Herrington, and T. B. Clarkson. Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries. J. Am. Coll. Cardiol. 20: 452-457, 1992. |
| 32. | Williams, J. K., M. R. Adams, and H. S. Klopfenstein. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 81: 1680-1687, 1990. |
| 33. | Ziegler, M. G. Postural hypotension. Annu. Rev. Med. 31: 239-245, 1980. |
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C. M. Foley, P. J. Mueller, E. M. Hasser, and C. M. Heesch Hindlimb unloading and female gender attenuate baroreflex-mediated sympathoexcitation Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1440 - R1447. [Abstract] [Full Text] [PDF]
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A. S. Jung, R. Harrison, K. H. Lee, J. Genut, D. Nyhan, E. M. Brooks-Asplund, A. A. Shoukas, J. M. Hare, and D. E. Berkowitz Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H600 - H607. [Abstract] [Full Text] [PDF]
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Q. Fu, S. Witkowski, K. Okazaki, and B. D. Levine Effects of gender and hypovolemia on sympathetic neural responses to orthostatic stress Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R109 - R116. [Abstract] [Full Text] [PDF]
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J. Gisolf, R. V. Immink, J. J. van Lieshout, W. J. Stok, and J. M. Karemaker Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method J Appl Physiol, May 1, 2005; 98(5): 1682 - 1690. [Abstract] [Full Text] [PDF]
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W. W. Waters, S. H. Platts, B. M. Mitchell, P. A. Whitson, and J. V. Meck Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H839 - H847. [Abstract] [Full Text] [PDF]
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S. M. Grenon, S. Hurwitz, N. Sheynberg, X. Xiao, B. Judson, C. D. Ramsdell, C. Kim, R. J. Cohen, and G. H. Williams Sleep restriction does not affect orthostatic tolerance in the simulated microgravity environment J Appl Physiol, November 1, 2004; 97(5): 1660 - 1666. [Abstract] [Full Text] [PDF]
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 A. Graebe, E. L. Schuck, P. Lensing, L. Putcha, and H. Derendorf Physiological, Pharmacokinetic, and Pharmacodynamic Changes in Space J. Clin. Pharmacol., August 1, 2004; 44(8): 837 - 853. [Abstract] [Full Text] [PDF]
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Y. Ishizaki, H. Fukuoka, T. Ishizaki, M. Kino, H. Higashino, N. Ueda, Y. Fujii, and Y. Kobayashi Measurement of inferior vena cava diameter for evaluation of venous return in subjects on day 10 of a bed-rest experiment J Appl Physiol, June 1, 2004; 96(6): 2179 - 2186. [Abstract] [Full Text] [PDF]
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S. M. Grenon, S. Hurwitz, N. Sheynberg, X. Xiao, C. D. Ramsdell, C. L. Mai, C. Kim, R. J. Cohen, and G. H. Williams Role of individual predisposition in orthostatic intolerance before and after simulated microgravity J Appl Physiol, May 1, 2004; 96(5): 1714 - 1722. [Abstract] [Full Text] [PDF]
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W. H. Cooke, K. L. Ryan, and V. A. Convertino Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans J Appl Physiol, April 1, 2004; 96(4): 1249 - 1261. [Abstract] [Full Text] [PDF]
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J. V. Meck, W. W. Waters, M. G. Ziegler, H. F. deBlock, P. J. Mills, D. Robertson, and P. L. Huang Mechanisms of postspaceflight orthostatic hypotension: low {alpha}1-adrenergic receptor responses before flight and central autonomic dysregulation postflight Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1486 - H1495. [Abstract] [Full Text] [PDF]
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X. Xiao, R. Mukkamala, N. Sheynberg, S. M. Grenon, M. D. Ehrman, T. J. Mullen, C. D. Ramsdell, G. H. Williams, and R. J. Cohen Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification J Appl Physiol, February 1, 2004; 96(2): 489 - 497. [Abstract] [Full Text] [PDF]
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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]
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A. Kamiya, D. Michikami, S. Iwase, J. Hayano, T. Kawada, M. Sugimachi, and K. Sunagawa {alpha}-Adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R151 - R157. [Abstract] [Full Text]
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A. Kamiya, D. Michikami, Q. Fu, S. Iwase, J. Hayano, T. Kawada, T. Mano, and K. Sunagawa Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1158 - H1167. [Abstract] [Full Text] [PDF]
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P-F. Migeotte, G. K. Prisk, and M. Paiva Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1995 - H2006. [Abstract] [Full Text] [PDF]
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J. R. Carter, C. A. Ray, and W. H. Cooke Vestibulosympathetic reflex during mental stress J Appl Physiol, October 1, 2002; 93(4): 1260 - 1264. [Abstract] [Full Text] [PDF]
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W. W. Waters, M. G. Ziegler, and J. V. Meck Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance J Appl Physiol, February 1, 2002; 92(2): 586 - 594. [Abstract] [Full Text] [PDF]
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D. C. Hatton, Q. Yue, J. Chapman, H. Xue, J. Dierickx, C. Roullet, S. Coste, J. B. Roullet, and D. A. McCarron Blood pressure and mesenteric resistance arterial function after spaceflight J Appl Physiol, January 1, 2002; 92(1): 13 - 17. [Abstract] [Full Text] [PDF]
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A. C Ertl, A. Diedrich, I. Biaggioni, B. D Levine, R. M. Robertson, J. F Cox, J. H Zuckerman, J. A Pawelczyk, C. A Ray, J. C Buckey Jr, et al. Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space J. Physiol., January 1, 2002; 538(1): 321 - 329. [Abstract] [Full Text] [PDF]
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B. D Levine, J. A Pawelczyk, A. C Ertl, J. F Cox, J. H Zuckerman, A. Diedrich, I. Biaggioni, C. A Ray, M. L Smith, S. Iwase, et al. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight J. Physiol., January 1, 2002; 538(1): 331 - 340. [Abstract] [Full Text] [PDF]
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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]
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F. Christ, J. Gamble, V. Baranov, A. Kotov, A. Chouker, M. Thiel, I. B. Gartside, C. M. Moser, J. Abicht, and K. Messmer Changes in microvascular fluid filtration capacity during 120 days of 6{degrees} head-down tilt J Appl Physiol, December 1, 2001; 91(6): 2517 - 2522. [Abstract] [Full Text] [PDF]
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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]
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D. L. Harm, R. T. Jennings, J. V. Meck, M. R. Powell, L. Putcha, C. P. Sams, S. M. Schneider, L. C. Shackelford, S. M. Smith, and P. A. Whitson Genome and Hormones: Gender Differences in Physiology: Invited Review: Gender issues related to spaceflight: a NASA perspective J Appl Physiol, November 1, 2001; 91(5): 2374 - 2383. [Abstract] [Full Text] [PDF]
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 J. V. Meck, C. J. Reyes, S. A. Perez, A. L. Goldberger, and M. G. Ziegler Marked Exacerbation of Orthostatic Intolerance After Long- vs. Short-Duration Spaceflight in Veteran Astronauts Psychosom Med, November 1, 2001; 63(6): 865 - 873. [Abstract] [Full Text] [PDF]
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P. J. Mills, J. V. Meck, W. W. Waters, D. D'Aunno, and M. G. Ziegler Peripheral Leukocyte Subpopulations and Catecholamine Levels in Astronauts as a Function of Mission Duration Psychosom Med, November 1, 2001; 63(6): 886 - 890. [Abstract] [Full Text] [PDF]
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J. K. Shoemaker, C. S. Hogeman, M. Khan, D. S. Kimmerly, and L. I. Sinoway Gender affects sympathetic and hemodynamic response to postural stress Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2028 - H2035. [Abstract] [Full Text] [PDF]
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C. D. Ramsdell, T. J. Mullen, G. H. Sundby, S. Rostoft, N. Sheynberg, N. Aljuri, M. Maa, R. Mukkamala, D. Sherman, K. Toska, et al. Midodrine prevents orthostatic intolerance associated with simulated spaceflight J Appl Physiol, June 1, 2001; 90(6): 2245 - 2248. [Abstract] [Full Text] [PDF]
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J. A. Pawelczyk, J. H. Zuckerman, C. G. Blomqvist, and B. D. Levine Regulation of muscle sympathetic nerve activity after bed rest deconditioning Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2230 - H2239. [Abstract] [Full Text] [PDF]
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V. A. Convertino Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R947 - R958. [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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C. A. Ray Effect of gender on vestibular sympathoexcitation Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1330 - R1333. [Abstract] [Full Text] [PDF]
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A. Kamiya, S. Iwase, D. Michikami, Q. Fu, and T. Mano Head-down bed rest alters sympathetic and cardiovascular responses to mental stress Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R440 - R447. [Abstract] [Full Text] [PDF]
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R. C. Looft-Wilson and C. V. Gisolfi Rat small mesenteric artery function after hindlimb suspension J Appl Physiol, April 1, 2000; 88(4): 1199 - 1206. [Abstract] [Full Text] [PDF]
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G. K. Prisk, A. R. Elliott, and J. B. West Sustained microgravity reduces the human ventilatory response to hypoxia but not to hypercapnia J Appl Physiol, April 1, 2000; 88(4): 1421 - 1430. [Abstract] [Full Text] [PDF]
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N. K. Muenter, D. E. Watenpaugh, W. L. Wasmund, S. L. Wasmund, S. A. Maxwell, and M. L. Smith Effect of sleep restriction on orthostatic cardiovascular control in humans J Appl Physiol, March 1, 2000; 88(3): 966 - 972. [Abstract] [Full Text] [PDF]
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A. Kamiya, S. Iwase, H. Kitazawa, T. Mano, O. L. Vinogradova, and I. B. Kharchenko Baroreflex control of muscle sympathetic nerve activity after 120 days of 6{degrees} head-down bed rest Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2000; 278(2): R445 - R452. [Abstract] [Full Text] [PDF]
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J. K. Shoemaker, C. S. Hogeman, and L. I. Sinoway Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R1084 - R1090. [Abstract] [Full Text] [PDF]
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D. Sigaudo, J.-O. Fortrat, A.-M. Allevard, A. Maillet, J.-M. Cottet-Emard, A. Vouillarmet, R. L. Hughson, G. Gauquelin-Koch, and C. Gharib Changes in the sympathetic nervous system induced by 42 days of head-down bed rest Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H1875 - H1884. [Abstract] [Full Text] [PDF]
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J. K. Shoemaker, C. S. Hogeman, U. A. Leuenberger, M. D. Herr, K. Gray, D. H. Silber, and L. I. Sinoway Sympathetic discharge and vascular resistance after bed rest J Appl Physiol, February 1, 1998; 84(2): 612 - 617. [Abstract] [Full Text] [PDF]
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 B. D. Levine, J. H. Zuckerman, and J. A. Pawelczyk Cardiac Atrophy After Bed-Rest Deconditioning : A Nonneural Mechanism for Orthostatic Intolerance Circulation, July 15, 1997; 96(2): 517 - 525. [Abstract] [Full Text]
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M. H. Khan, A. R. Kunselman, U. A. Leuenberger, W. R. Davidson Jr., C. A. Ray, K. S. Gray, C. S. Hogeman, and L. I. Sinoway Attenuated sympathetic nerve responses after 24 hours of bed rest Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2210 - H2215. [Abstract] [Full Text] [PDF]
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B. D. Levine, J. A. Pawelczyk, A. C. Ertl, J. F. Cox, J. H. Zuckerman, A. Diedrich, I. Biaggioni, C. A. Ray, M. L. Smith, S. Iwase, et al. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight J. Physiol., December 3, 2001; (2001) 200101257. [Abstract] [PDF]
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