Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.     

Alpha-adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans

Space-flight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), cause cardiovascular deconditioning in humans. Because sympathetic vasoconstriction plays a very important role in circulation, we examined whether HDBR impairs alpha-adrenergic vascular responsiveness to sympathetic nerve activity. We subjected eight healthy volunteers to 14 days of HDBR and before and after HDBR measured calf muscle sympathetic nerve activity (MSNA; microneurography) and calf blood flow (venous occlusion plethysmography) during sympathoexcitatory stimulation (rhythmic handgrip exercise). HDBR did not change the increase in total MSNA (P = 0.97) or the decrease in calf vascular conductance (P = 0.32) during exercise, but it did augment the increase in calf vascular resistance (P = 0.0011). HDBR augmented the transduction gain from total MSNA into calf vascular resistance, assessed as the least squares linear regression slope of vascular resistance on total MSNA (0.05 +/- 0.02 before HDBR, 0.20 +/- 0.06 U.min-1.burst-1 after HDBR, P = 0.0075), but did not change the transduction gain into calf vascular conductance (P = 0.41). Our data indicate that alpha-adrenergic vascular responsiveness to sympathetic nerve activity is preserved in the supine position after HDBR in humans.     

Increase in epinephrine-induced responsiveness during microgravity simulated by head-down bed rest in humans.

The epinephrine (Epi)-induced effects on the sympathetic nervous system (SNS) and metabolic functions were studied in men before and during a decrease in SNS activity achieved through simulated microgravity. Epi was infused at 3 graded rates (0.01, 0.02, and 0. 03 microg. kg(-1). min(-1) for 40 min each) before and on the fifth day of head-down bed rest (HDBR). The effects of Epi on the SNS (assessed by plasma norepinephrine levels and spectral analysis of systolic blood pressure and heart rate variability), on plasma levels of glycerol, nonesterified fatty acids (NEFA), glucose and insulin, and on energy expenditure were evaluated. HDBR decreased urinary norepinephrine excretion (28.1 +/- 4.2 vs. 51.5 +/- 9.1 microg/24 h) and spectral variability of systolic blood pressure in the midfrequency range (16.3 +/- 1.9 vs. 24.5 +/- 0.9 normalized units). Epi increased norepinephrine plasma levels (P < 0.01) and spectral variability of systolic blood pressure (P < 0.009) during, but not before, HDBR. No modification of Epi-induced changes in heart rate and systolic and diastolic blood pressures were observed during HDBR. Epi increased plasma glucose, insulin, and NEFA levels before and during HDBR. During HDBR, the Epi-induced increase in plasma glycerol and lactate levels was more pronounced than before HDBR (P < 0.005 and P < 0.001, respectively). Epi-induced energy expenditure was higher during HDBR (P < 0.02). Our data suggest that the increased effects of Epi during simulated microgravity could be related to both the increased SNS response to Epi infusion and/or to the beta-adrenergic receptor sensitization of end organs, particularly in adipose tissue and skeletal muscle.     

Effect of head-down bed rest on the neuroendocrine response to orthostatic stress in physically fit men

The role of neuroendocrine responsiveness in the development of orthostatic intolerance after bed rest was studied in physically fit subjects. Head-down bed-rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic training. The standing test was performed before, after training and on day 4 of the HDBR. Orthostatic intolerance was observed in one subject before and after training. The blood pressure response after training was enhanced (mean BP increments 18+/-2 vs. 13+/- 2 mm Hg, p<0.05, means +/- S.E.M.), although noradrenaline response was diminished (1.38+/-0.18 vs. 2.76+/-0.25 mol.l(-1), p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP response was blunted, and noradrenaline as well as plasma renin activity (PRA) responses were augmented (NA 3.10+/-0.33 mol.l(-1), p<0.001; PRA 2.98+/-1.12 vs. 0.85+/-0.15 ng.ml(-1), p<0.05). Plasma noradrenaline, adrenaline and aldosterone responses in orthostatic intolerant subjects were similar to the tolerant group. We conclude that six weeks of training attenuated the sympathetic response to standing and had no effect on the orthostatic tolerance. In orthostatic intolerance the BP response induced by subsequent HDBR was absent despite an enhanced sympathetic response.     

Responses of muscle sympathetic nerve activity to static handgrip exercise after 14 days of exposure to simulated microgravity

Decrease in muscle perfusion affects on cardiovascular response to exercise. Muscle hypoperfusion enhances the increase in blood pressure responses to exercise. Muscle perfusion depends not only on central blood pressure but also how fit the active muscle is above or below the heart level; muscle perfusion decreases as arm is elevated. Static exercise increases muscle sympathetic nerve activity (MSNA) innervating vessels in non-active muscles. The exercise-induced increase in MSNA is mainly mediated by stimulating chemosensitive muscle afferents in active muscles. However, the effect of arm elevation on MSNA during forearm exercise is not examined. On the other hand, space flight and simulated microgravity exposure causes reduction in muscle blood flow, suggesting chronic muscle hypoperfused condition during simulated microgravity. Therefore, there is a possibility that arm elevation after microgravity exposure alters MSNA responsiveness during exercise. However, arm elevation effect after exposure to simulated microgravity is not examined.     

Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.     

Responses of sympathoadrenal and renin angiotensin systems to stress stimuli in humans during real and simulated microgravity

Changes of plasma hormone levels were investigated in human subjects after exposure to physical exercise (WL) and insulin induced hypoglycemia (ITT) during apace flight or after head down bed rest (HDBR). Exaggerated responses of plasma epinephrine (EPI), norepinephrine (NE) and aldosterone (ALD) were observed after WL during space flight as compared to preflight response. Hypoglycemia during space flight induced attenuated responses of EPI, NE and augmented response of ALD. Exposure to WL during HDBR was followed by significantly exaggerated responses of plasma EPI, NE, ALD, PRA and cortisol. In HDBR the responses of plasma EPI, NE and cortisol were reduced and PRA response was exaggerated during ITT. These data indicate that hormonal responses to ITT and WL are similar at real and simulated microgravity.     

Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.     

Neurovascular responses to mental stress in the supine and upright postures.

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.     

Sympathetic nervous activity decreases during head-down bed rest but not during microgravity.

We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy subjects were studied before and during HDBR of 2-wk duration, as well as during an ambulatory study period of a similar length. Platelet norepinephrine concentrations (half-life = 2 days) were studied in five cosmonauts, 2 wk before launch, within 12 h after landing after 11-12 days of flight, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P < 0.001), whereas there were no significant changes when subjects were ambulatory. Platelet epinephrine did not change during HDBR. During microgravity, platelet norepinephrine and epinephrine increased in four of the five cosmonauts. Platelet norepinephrine concentrations expressed in percentage of preflight and pre-HDBR values, respectively, were significantly different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs. 60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet norepinephrine and epinephrine response during spaceflight flight is most likely related to the concomitant decrease in plasma volume. HDBR cannot be applied to simulate changes in sympathoadrenal activity during microgravity.     

Arterial baroreflex control of sympathetic vasoconstrictor traffic and orthostatic intolerance after head-down bed rest

The purpose of the present study is to examine the changes in the arterial baroreflex control of muscle sympathetic nerve activity (MSNA) after head-down bed rest (HDBR), in relation to orthostatic hypotension after HDBR. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, with monitoring MSNA, heart rate and blood pressure. We calculated the gain of the arterial baroreflex control of MSNA, and compared the gains between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.     

Effect of change in intrathoracic pressure on thermoregulatory responses during -6 degree head-down bed rest

We investigated the effect of change in intrathoracic pressure by total body negative pressure (TBNP) or positive pressure (TBPP) on thermoregulatory responses during -6 degree head-down bed rest (HDBR). Eight healthy male subjects participated to three of the following interventions in a randomised sequence: 1) HDBR, 2) HDBR with TBNP of -15 cmH2O, 3) HDBR with TBPP of +15 cmH2O. A rapid decrease of cutaneous blood flow occurred after the start of TBNP. In contrast, cutaneous blood flow increased slightly at TBPP. Sweat rate decreased immediately after the start of TBNP. Immediately after the TBPP was started, tympanic temperature greatly decreased. It is concluded that combination of HDBR and intrathoracic pressure changes thermoregulatory responses through the cardiopulmonary baroreceptor to reduce the wall stretch.     

Autonomic and vascular responses to reduced limb perfusion.

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 +/- 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.     

Hemodynamic and sympathoadrenal responses to mental stress during nitric oxide synthesis inhibition

Cardiovascular and sympathoadrenal responses to a reproducible mental stress test were investigated in eight healthy young men before and during intravenous infusion of the nitric oxide (NO) synthesis inhibitor N-monomethyl-L-arginine (L-NMMA). Before L-NMMA, stress responses included significant increases in heart rate, mean arterial pressure, and cardiac output (CO) and decreases in systemic and forearm vascular resistance. Arterial plasma norepinephrine (NE) increased. At rest after 30 min of infusion of L-NMMA (0.3 mg.kg(-1).min(-1) iv), mean arterial pressure increased from 98 +/- 4 to 108 +/- 3 mmHg (P <0.001) because of an increase in systemic vascular resistance from 12.9 +/- 0.5 to 18.5 +/- 0.9 units (P <0.001). CO decreased from 7.7 +/- 0.4 to 5.9 +/- 0.3 l/min (P <0.01). Arterial plasma NE decreased from 2.08 +/- 0.16 to 1.47 +/- 0.14 nmol/l. Repeated mental stress during continued infusion of L-NMMA (0.15 mg.kg(-1).min(-1)) induced qualitatively similar cardiovascular responses, but there was a marked attenuation of the increase in mean arterial blood pressure, resulting in similar "steady-state" blood pressures during mental stress without and with NO blockade. Increases in heart rate and CO were attenuated, but stress-induced decreases in systemic and forearm vascular resistance were essentially unchanged. Arterial plasma NE increased less than during the first stress test. Thus the increased arterial tone at rest during L-NMMA infusion is compensated for by attenuated increases in blood pressure during mental stress, mainly through a markedly attenuated CO response and suppressed sympathetic nerve activity.     

Combined heat and mental stress alters neurovascular control in humans

This study examined the effect of combined heat and mental stress on neurovascular control. We hypothesized that muscle sympathetic nerve activity (MSNA) and forearm vascular responses to mental stress would be augmented during heat stress. Thirteen subjects performed 5 min of mental stress during normothermia (Tcore; 37 ± 0°C) and heat stress (38 ± 0°C). Heart rate, mean arterial pressure (MAP), MSNA, forearm vascular conductance (FVC; venous occlusion plethysmography), and forearm skin vascular conductance (SkVCf; via laser-Doppler) were analyzed. Heat stress increased heart rate, MSNA, SkVCf, and FVC at rest but did not change MAP. Mental stress increased MSNA and MAP during both thermal conditions; however, the increase in MAP during heat stress was blunted, whereas the increase in MSNA was accentuated, compared with normothermia (time × condition; P < 0.05 for both). Mental stress decreased SkVCf during heat stress but not during normothermia (time × condition, P < 0.01). Mental stress elicited similar increases in heart rate and FVC during both conditions. In one subject combined heat and mental stress induced presyncope coupled with atypical blood pressure and cutaneous vascular responses. In conclusion, these findings indicate that mental stress elicits a blunted increase of MAP during heat stress, despite greater increases in total MSNA and cutaneous vasoconstriction. The neurovascular responses to combined heat and mental stress may be clinically relevant to individuals frequently exposed to mentally demanding tasks in hyperthermic environmental conditions (i.e., soldiers, firefighters, and athletes).     

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ～34°C and skin surface cooling ～12-15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ～30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals.     

Altered hormonal regulation and blood flow distribution with cardiovascular deconditioning after short-duration head down bed rest.

This study tested the hypothesis that cardiovascular and hormonal responses to lower body negative pressure (LBNP) would be altered by 4-h head down bed rest (HDBR) in 11 healthy young men. In post-HDBR testing, three subjects failed to finish the protocol due to presyncopal symptoms, heart rate was increased during LBNP compared with pre-HDBR, mean arterial blood pressure was elevated at 0, -10, and -20 mmHg and reduced at -40 mmHg, central venous pressure (CVP) and cardiac stroke volume were reduced at all levels of LBNP. Plasma concentrations of renin, angiotensin II, and aldosterone were significantly lower after HDBR. Renin and angiotensin II increased in response to LBNP only post-HDBR. There was no effect of HDBR or LBNP on norepinephrine while epinephrine tended to increase at -40 mmHg post-HDBR (P = 0.07). Total blood volume was not significantly reduced. Splanchnic blood flow taken from ultrasound measurement of the portal vein was higher at each level of LBNP post-compared with pre-HDBR. The gain of the cardiopulmonary baroreflex relating changes in total peripheral resistance to CVP was increased after HDBR, but splanchnic vascular resistance was actually reduced. These results are consistent with our hypothesis and suggest that cardiovascular instability following only 4-h HDBR might be related to altered hormonal and/or neural control of regional vascular resistance. Impaired ability to distribute blood away from the splanchnic region was associated with reduced stroke volume, elevated heart rate, and the inability to protect mean arterial pressure.