Aspects of control of the cardiovascular-respiratory system during orthostatic stress induced by lower body negative pressure

This paper considers a model developed to study the cardiovascular control system response to orthostatic stress as induced by two variations of lower body negative pressure (LBNP) experiments. This modeling approach has been previously applied to study control responses to transition from rest to aerobic exercise, to transition to non-REM sleep and to orthostatic stress as produced by the head up tilt (HUT) experiment. LBNP induces a blood volume shift because negative pressure changes the volume loading characteristics of the compartment which is subject to the negative pressure. This volume shift induces a fall in blood pressure which must be counteracted by a complicated control response involving a variety of mechanisms of the cardiovascular control system. There are a number of medical issues connected to these questions such as orthostatic intolerance in the elderly resulting in dizziness or fainting during the transition from sitting to standing. The model presented here is used to study the interaction of changes in systemic resistance, unstressed venous volume, venous compliance, heart rate, and contractility in the control of orthostatic stress. The overall short term response depends on a combination of these physiological reactions which may vary from individual to individual. There remain open questions about which factors have greater importance. The model simulations are compared to experimental data collected for LBNP exerted from the hips to feet and from ribs to feet.     

Cardiovascular responses to an orthostatic challenge and electrical-stimulation-induced leg muscle contractions in individuals with paraplegia

The purpose of this study was to investigate the cardiovascular and haemodynamic responses that occur during moderate orthostatic challenge in people with paraplegia, and the effect of electrical stimulation (ES)-induced leg muscle contractions on their responses to orthostatic challenge. Eight males with complete spinal lesions between the 5th and 12th thoracic vertebrae (PARA) and eight able-bodied individuals (AB) volunteered for this study. Changes in heart rate (fc), stroke volume (SV), cardiac output (Qc), mean arterial pressure (MAP), total peripheral resistance (TPR), limb volumes and indices of neural modulation of fc, [parasympathetic (PNS) and sympathetic (SNS) nervous system indicators] were assessed during: (1) supine rest (REST), (2) REST with lower-body negative pressure at -30 torr (LBNP -30, where 1 torr = 133.32 N/m2), and (3) for PARA only, LBNP -30 with ES-induced leg muscle contractions (LBNP + ES). LBNP -30 elicited a decrease in SV (by 23% and 22%), Qc (by 15% and 18%) and the PNS indicator, but an increase in fc (by 10% and 9%), TPR (by 23% and 17%) and calf volume (by 1.51% and 4.04%) in both PARA and AB subjects, respectively. The SNS indicator was increased in the AB group only. Compared to LBNP -30, LBNP + ES increased SV (by 20%) and Qc (by 16%), and decreased TPR (by 12%) in the PARA group. MAP was unchanged from REST during all trials, for both groups. The orthostatic challenge induced by LBNP -30 elicited similar cardiovascular adaptations in PARA and AB subjects. ES-induced muscle contractions during LBNP -30 augmented the cardiovascular responses exhibited by the PARA group, probably via reactivation of the skeletal muscle pump and improved venous return.     

Construction of a lower body negative pressure chamber

Lower body negative pressure (LBNP) is an established and important technique used to physiologically stress the human body, particularly the cardiovascular system. LBNP is most often used to simulate gravitational stress, but it has also been used to simulate hemorrhage, alter preload, and manipulate baroreceptors. During experimentation, the consequences of LBNP and the reflex increases in heart rate and blood pressure can be manipulated and observed in a well-controlled manner, thus making LBNP an important research tool. Numerous laboratories have developed LBNP devices for use in research settings, and a few devices are commercially available. However, it is often difficult for new users to find adequately described design plans. Furthermore, many available plans require sophisticated and expensive materials and/or technical support. Therefore, we have created an affordable design plan for a LBNP chamber. The purpose of this article was to share our design template with others. In particular, we hope that this information will be of use in academic and research settings. Our pressure chamber has been stress tested to 100 mmHg below atmospheric pressure and has been used successfully to test orthostatic tolerance and physiological responses to -50 mmHg.     

Vestibulosympathetic reflex during orthostatic challenge in aging humans

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.     

Teaching fluid shifts during orthostasis using a classic paper by Foux et al

Hypovolemic and orthostatic challenge can be simulated in humans by the application of lower body negative pressure (LBNP), because this perturbation leads to peripheral blood pooling and, consequently, central hypovolemia. The classic paper by Foux and colleagues clearly shows the effects of orthostasis simulated by LBNP on fluid shifts and homeostatic mechanisms. The carefully carried out experiments reported in this paper show the interplay between different physiological control systems to ensure blood pressure regulation, failure of which could lead to critical decreases in cerebral blood flow and syncope. Here, a teaching seminar for graduate students is described that is designed in the context of this paper and aimed at allowing students to learn how Foux and colleagues have advanced this field by addressing important aspects of blood regulation. This seminar is also designed to put their research into perspective by including important components of LBNP testing and protocols developed in subsequent research in the field. Learning about comprehensive protocols and carefully controlled studies can reduce confounding variables and allow for an optimal analysis and elucidation of the physiological responses that are being investigated. Finally, in collaboration with researchers in mathematical modeling, in the future, we will incorporate the concepts of applicable mathematical models into our curriculum.     

四周尾部悬吊致大鼠立位耐力不良

目的:观察中期(4周)尾部悬吊大鼠在立位应激下的心血管反应。方法:采用本实验室改进的尾部悬吊方法,利用头高位倾斜和下体负压模拟立位应激,通过股动脉插管和心电图记录检测大鼠血压和心率改变。结果:与对照组相比,4周尾部悬吊(SUS)大鼠体重下降及后肢承重骨骼肌萎缩;其静息血压和心率与对照组(CON)相比无明显差别(P0.05);在两组大鼠中,头高位倾斜和下体负压均可导致血压降低和心率加快,但SUS大鼠平均动脉压下降幅度与CON大鼠相比显著增大(P0.05),而两组的心率增快幅度并无明显差别(P0.05)。结论:4周尾部悬吊大鼠在立位应激下维持血压稳定的能力减弱,可用于中期失重/模拟失重后立位耐力不良机理的研究。     

Effect of skin surface cooling on central venous pressure during orthostatic challenge

Orthostatic stress leads to a reduction in central venous pressure (CVP), which is an index of cardiac preload. Skin surface cooling has been shown to improve orthostatic tolerance, although the mechanism resulting in this outcome is unclear. One possible mechanism may be that skin surface cooling attenuates the drop in CVP during an orthostatic challenge, thereby preserving cardiac filling. To test this hypothesis, CVP, arterial blood pressure, heart rate, and skin blood flow, as well as skin and sublingual temperatures, were recorded in nine healthy subjects during lower body negative pressure (LBNP) in both normothermic and skin surface cooling conditions. Cardiac output was also measured via acetylene rebreathing. Progressive LBNP was applied at -10, -15, -20, and -40 mmHg at 5 min/stage. Before LBNP, skin surface cooling lowered mean skin temperature, increased CVP, and increased mean arterial blood pressure (all P < 0.001) but did not change mean heart rate (P = 0.38). Compared with normothermic conditions, arterial blood pressure remained elevated throughout progressive LBNP. Although progressive LBNP decreased CVP under both thermal conditions, during cooling CVP at each stage of LBNP was significantly greater relative to normothermia. Moreover, at higher levels of LBNP with skin cooling, stroke volume was significantly greater relative to normothermic conditions. These data indicate that skin surface cooling induced an upward shift in CVP throughout LBNP, which may be a key factor for preserving preload, stroke volume, and blood pressure and improving orthostatic tolerance.     

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.     

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.     

Relationship between atrial natriuretic peptide (ANP), renin (PRA), aldosterone (PAC), hemodynamic responses to lower body negative pressure (LBNP) and +Gz tolerance

The redistribution of a certain thoracic blood volume to the lower parts of the body and decrease of the venous return of blood to the heart during lower body negative pressure leads to the central hypovolemia and the deactivation of cardiopulmonary and arterial baroreceptors. Many compensatory mechanisms are involved during central hypovolemia, which is also reflected by the changes in the secretion of different vasoactive hormones. Due to this fact the LBNP stimulus is widely used for the investigation of regulatory (compensatory) mechanisms in cardiovascular system providing deeper understanding of orthostatic reaction. Recently several papers were published on application of this experimental model for +Gz acceleration tolerance assessment. The purpose of this study was evaluate the possible dependence between the changes of ANP secretion, renin-angiotensin-aldosterone system activity, the changes of some hemodynamic parameters during the model of gravitational stress i.e. LBNP exposure and +Gz acceleration tolerance.     

Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.

The purpose of this project was to test the hypothesis that increases in muscle sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated in heat-stressed individuals. To accomplish this objective, MSNA was measured during graded lower body negative pressure (LBNP) in nine subjects under normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, -6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating caused significant increases in sublingual temperature, skin blood flow, sweat rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure (P > 0.05). Progressive LBNP induced significant increases in MSNA in both thermal conditions. However, during the heat stress trial, increases in MSNA at LBNP levels higher than -9 mmHg were greater compared with during the same LBNP levels in normothermia (all P < 0.05). These data suggest that the increase in MSNA to orthostatic stress is not attenuated but rather accentuated in heat-stressed humans.     

Mechanisms of changes in human hemodynamics under the conditions of microgravity and prognosis of postflight orthostatic stability

The mechanisms of hemodynamic responses to orthostatic stresses and orthostatic stability (OS) of cosmonauts were studied before and after short-and long-term spaceflights (SFs) using orthostatic tests, as well as before, during, and after SFs using ultrasonic methods in tests with exposure to lower body negative pressure (LBNP). The capacitance and distensibility of the veins of the lower extremities were studied using occlusive air plethysmography before, during, and after SFs of different durations. A stay in microgravity has been proved to result in detraining of, mainly, the vascular mechanisms of compensating orthostatic perturbations. It has been established that the decrease in OS under the influence of microgravity is determined by a reduction of the vasoconstrictive ability of large blood vessels of the lower extremities; an increase in venous distensibility and capacitance of the legs; and an impairment of blood flow regulation, which leads to a cerebral blood flow deficit in orthostatic stresses, and of the initial individual OS before the flight. The results of preflight studies of hemodynamics by ultrasonic methods at LBNP and the data of orthostatic tests before SFs make it possible to predict the degree of decrease of OS after an SF proceeding in the normal mode. At the same time, the data of ultrasonic blood flow examination provide more a accurate estimation of OS and make it possible to assess the physiological reserves of hemodynamic regulation and to reveal the loss of regulation capacity even in cases where integrated indices (heart rate and blood pressure) are within the normal ranges.     

Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic tests after 4 days in the head-down tilt position or confinement

The first objective of this study was to confirm that 4 days of head-down tilt (HDT) were sufficient to induce orthostatic intolerance, and to check if 4 days of physical confinement may also induce orthostatic intolerance. Evidence of orthostatic intolerance during tilt-up tests was obtained from blood pressure and clinical criteria. The second objective was to quantify the arterial and venous changes associated with orthostatic intolerance and to check whether abnormal responses to the tilt test and lower body negative pressure (LBNP) may occur in the absence of blood pressure or clinical signs of orthostatic intolerance. The cerebral and lower limb arterial blood flow and vascular resistance, the flow redistribution between these two areas, and the femoral vein distension were assessed during tilt-up and LBNP by ultrasound. Eight subjects were given 4 days of HDT and, 1 month later, 4 days of physical confinement. Tilt and LBNP test were performed pre- and post-HDT and confinement. Orthostatic intolerance was significantly more frequent after HDT (63%) than after confinement (25%, P<0.001). Cerebral haemodynamic responses to tilt-up and LBNP tests were similar pre- and post-HDT or confinement. Conversely, during both tilt and LBNP tests the femoral vascular resistances increased less (P<0.002), and the femoral blood flow reduced less (P<0.001) after HDT than before HDT or after confinement. The cerebral to femoral blood flow ratio increased less after HDT than before (P<0.002) but remained unchanged before and after confinement. This ratio was significantly more disturbed in the subjects who did not complete the tilt test. The femoral superficial vein was more distended during post-HDT LBNP than pre-HDT or after confinement (P<0.01). In conclusion, 4 days of HDT were enough to alter the lower limb arterial vasoconstriction and venous distensibility during tilt-up and LBNP, which reduced the flow redistribution in favour of the brain in all HDT subjects. Confinement did not alter significantly the haemodynamic responses to orthostatic tests. The cerebral to femoral blood flow ratio measured during LBNP was the best predictor of orthostatic intolerance. Accepted: 12 December 1997     

Comparison of cardiovascular responses between lower body negative pressure and head-up tilt.

To investigate local blood-flow regulation during orthostatic maneuvers, 10 healthy subjects were exposed to -20 and -40 mmHg lower body negative pressure (LBNP; each for 3 min) and to 60 degrees head-up tilt (HUT; for 5 min). Measurements were made of blood flow in the brachial (BF(brachial)) and femoral arteries (BF(femoral)) (both by the ultrasound Doppler method), heart rate (HR), mean arterial pressure (MAP), cardiac stroke volume (SV; by echocardiography), and left ventricular end-diastolic volume (LVEDV; by echocardiography). Comparable central cardiovascular responses (changes in LVEDV, SV, and MAP) were seen during LBNP and HUT. During -20 mmHg LBNP, -40 mmHg LBNP, and HUT, the following results were observed: 1) BF(brachial) decreased by 51, 57, and 41%, and BF(femoral) decreased by 40, 53, and 62%, respectively, 2) vascular resistance increased in the upper limb by 110, 147, and 85%, and in the lower limb by 76, 153, and 250%, respectively. The increases in vascular resistance were not different between the upper and lower limbs during LBNP. However, during HUT, the increase in the lower limb was much greater than that in the upper limb. These results suggest that, during orthostatic stimulation, the vascular responses in the limbs due to the cardiopulmonary and arterial baroreflexes can be strongly modulated by local mechanisms (presumably induced by gravitational effects).     

Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment

In this article, we intentionally present exclusively the results of our recent studies of arterial and venous hemodynamics as predictors of human orthostatic tolerance during space flight and after the return to Earth. The possibility of in-flight orthostatic tolerance prediction by arterial hemodynamic responses to the lower body negative pressure (LBNP) and venous hemodynamic changes in response to occlusion of the lower extremities is demonstrated. For the first time, three levels of cerebral blood flow deficits during the determination of orthostatic tolerance in the course of the LBNP test performed in microgravity. We offer quantitative arguments for the dependence of the cerebral blood flow deficit on the degree of tolerance of the LBNP test. Patterns of arterial hemodynamics during LBNP were successfully used to diagnose the actual orthostatic tolerance and to follow its trend during flight, which testifies to the possibility of predicting orthostatic tolerance changes in an individual cosmonaut during space flight. Occlusion plethysmography of the legs revealed three levels of response of the most informative venous parameters (capacity, distensibility, and rate of filling) of the lower extremities correlated to the severity of decrease in orthostatic tolerance.     

Orthostatic hypotension in aging humans

We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP.     

Validity of auscultatory and Penaz blood pressure measurements during profound heat stress alone and with an orthostatic challenge

Despite frequent reporting of blood pressure (BP) during profound passive heat stress, both with and without a hypotensive challenge, the method by which BP is measured often varies between laboratories. It is unknown whether auscultatory and finger BP measures accurately reflect intra-arterial BP during dynamic changes in cardiac output and peripheral resistance associated with the aforementioned conditions. The purpose of this investigation was to test the hypothesis that auscultatory BP measured at the brachial artery, and finger BP measured by the Penaz method, are valid measures of intra-arterial BP during a passive heat stress and a heat-stressed orthostatic challenge, via lower body negative pressure (LBNP). Absolute (specific aim 1) and the change in (specific aim 2) systolic (SBP), diastolic (DBP), and mean BPs (MBP) were compared at normothermia, after a core temperature increase of 1.47 ± 0.09°C, and during subsequent LBNP. Heat stress did not change auscultatory SBP (6 ± 11 mmHg; P = 0.16), but Penaz SBP (-22 ± 16 mmHg; P < 0.001) and intra-arterial SBP (-11 ± 13 mmHg P = 0.017) decreased. In contrast, DBP and MBP did not differ between methods throughout heat stress. Compared with BP before LBNP, the magnitude of the reduction in BP with all three methods was similar throughout LBNP (P > 0.05). In conclusion, auscultatory SBP and Penaz SBP failed to track the decrease in intra-arterial SBP that occurred during the profound heat stress, while decreases in arterial BP during an orthostatic challenge are comparable between methodologies.     

Cardiovascular response to lower body negative pressure before and after 20 days horizontal bed rest

To evaluate the effects of 20 days bed rest (BR) on cardiovascular system in normal subjects, left ventricular (LV) echocardiography and vascular ultrasound of the common carotid artery and abdominal aorta were performed during rest and a supine lower body negative pressure (LBNP) test in 14 healthy volunteers (mean age: 22 years) before and after BR. After BR, heart rates (HR) at rest and during LBNP (-40 mmHg) increased. In contrast, LV dimensions, stroke volume, and blood pressures decreased both at rest and during LBNP. Also LBNP tolerance time decreased after BR. Although resting cardiac output (CO) and abdominal aortic flow decreased after bed rest, CO and abdominal aortic flow were unchanged during LBNP comparing before and after BR. Common carotid artery flows both at rest and during LBNP showed no change after BR. LBNP did not increase HR before BR, but increased HR prominently after BR. In conclusion, LBNP tolerance time and LV size during LBNP decreased after BR, suggesting orthostatic intolerance due to a decreased blood volume. However, CO and flow in the abdominal aorta and common carotid artery during LBNP were similar before and after BR due to a compensatory increase after BR.     

Sex differences in hemodynamic and sympathetic neural firing patterns during orthostatic challenge in humans

Recent evidence suggests that young men and women may have different strategies for regulating arterial blood pressure, and the purpose of the present study was to determine if sex differences exist in diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA) relations during simulated orthostatic stress. We hypothesized that young men would demonstrate stronger DAP-MSNA coherence and a greater percentage of "consecutive integrated bursts" during orthostatic stress. Fourteen men and 14 women (age 23 ± 1 yr) were examined at rest and during progressive lower body negative pressure (LBNP; -5 to -40 mmHg). Progressive LBNP did not alter mean arterial pressure (MAP) in either sex. Heart rate increased and stroke volume decreased to a greater extent during LBNP in women (interactions, P < 0.05). DAP-MSNA coherence was strong (i.e., r ≥ 0.5) at rest and increased throughout all LBNP stages in men. In contrast, DAP-MSNA coherence was lower in women, and responses to progressive LBNP were attenuated compared with men (time × sex, P = 0.029). Men demonstrated a higher percentage of consecutive bursts during all stages of LBNP (sex, P < 0.05), although the percentage of consecutive bursts increased similarly during progressive LBNP between sexes. In conclusion, men and women demonstrate different firing patterns of integrated MSNA during LBNP that appear to be related to differences in DAP oscillatory patterns. Men tend to have more consecutive bursts, which likely contribute to a stronger DAP-MSNA coherence. These findings may help explain why young women are more prone to orthostatic intolerance.     

Skin surface cooling improves orthostatic tolerance in normothermic individuals

Previous studies suggest that skin surface cooling (SSC) preserves orthostatic tolerance; however, this hypothesis has not been experimentally tested. Thus the purpose of this project was to identify whether SSC improves orthostatic tolerance in otherwise normothermic individuals. Eight subjects underwent two presyncope limited graded lower-body negative pressure (LBNP) tolerance tests. On different days, and randomly assigned, LBNP tolerance was assessed under control conditions and during SSC (perfused 16 degrees C water through tube-lined suit worn by each subject). Orthostatic tolerance was significantly elevated in each individual due to SSC, as evidenced by a significant increase in a standardized cumulative stress index (normothermia 564 +/- 58 mmHg.min; SSC 752 +/- 58 mmHg.min; P < 0.05). At most levels of LBNP, blood pressure during the SSC tolerance test was significantly greater than during the control test. Furthermore, the reduction in cerebral blood flow velocity was attenuated during some of the early stages of LBNP for the SSC trial. Plasma norepinephrine concentrations were significantly higher during LBNP with SSC, suggesting that SSC may improve orthostatic tolerance through increased sympathetic activity. These data demonstrate that SSC is effective in improving orthostatic tolerance in otherwise normothermic individuals.