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[Microgravity and autonomic nervous system].

How microgravity influences autonomic function is still under investigation. Microgravity induces neuro-vestibular alterations and body fluid shift, and these two changes cause "space motion sickness(SMS)" and cardiovascular deconditioning. "Space motion sickness" is a autonomic syndrome that exhibits nausea, vomiting, headache, anorexia, pallor etc., whose incidence in Space Shuttle mission reaches 67.1%. There are several hypotheses for SMS mechanism: 1) sensory conflict, 2) fluid shift, 3) otolith asymmetry, 4) space orientation readaptation, 5) otolith tilt-translation reinterpretation, and these hypotheses are considered to be combined together to cause SMS. After space flight, 64% of the astronauts suffer from orthostatic intolerance, which is defined as incompletion of 15 min of 70 degrees head-up tilt. Several causes for the deconditioning have been hypothesized, dehydration followed by fluid shift, altered gain for baroreflex sensitivity, decreased venous capacitance, etc. In our previous studies, we recorded muscle sympathetic nerve activity(MSNA) by microneurography under simulated and actual microgravity conditions. Parabolic flight, which induces 20 sec of actual microgravity, suppressed MSNA to 50%. Head-out water immersion suppressed MSNA to 20% while gradual recovery was observed during 3 hours of immersion. Dry immersion for 3 days revealed that MSNA was enhanced after simulated microgravity while the response to orthostasis was unchanged. Bed rest for 6, 14, and 120 days and Neurolab Project clarified the same tendency for longer duration of simulated microgravity. These alterations in MSNA might be attributed to the development of cardiovascular deconditioning after microgravity exposure.

Autonomic Nervous System↗

Twenty four hours head-down tilt decreases arterial baroreflex function in conscious rat.

In human zero gravity induces a cardiovascular deconditioning. The transfer of blood from the periphery to the thoracic compartment, occuring immediately at the beginning of the exposure to microgravity seems to be involved in this phenomenon. We have previously shown that LBNP (-40 mm Hg) produced an exaggerated heart rate response at the end of 24 hours of bed rest without modification of the cardiopulmonary receptors in human. Some other studies have shown that microgravity induces an impairment of the baroreflex sensitivity in human, but its involvement in the cardiovascular deconditioning is not completely understood. The aim of this study was to determine the modification of the arterial baroreflex using a model of simulated weightlessness in conscious rats during the exposure to microgravity.

Animals↗

Renal, endocrine, and cardiovascular responses to bed rest in male subjects on a constant diet.

BACKGROUND: Exposure to actual and simulated microgravity induces cardiovascular deconditioning through a variety of factors. Although the mechanisms involved remain uncertain, one involves alterations in volume-regulating systems--the hypothesis being tested in this study. To maximize our ability to detect subtle changes in the volume-regulating systems, subjects were studied on a high-average salt intake to maximally suppress these systems basally. METHODS: Fourteen healthy male subjects underwent 14-day head-down tilt bed rest (HDTB) during which a constant 200 mEq sodium, 100 mEq potassium diet was maintained. Daily 24-hour urine collection was performed; plasma renin activity, serum aldosterone, plethysmography, and cardiovascular system identification were performed during a control period (pre-HDTB) and at the end of HDTB (end HDTB). RESULTS: Sodium excretion increased initially (pre-HDTB = 182.8 +/- 10.4 mEq/total volume; early HDTB = 236.4 +/- 13.0; p = .002) and then returned to baseline values. Potassium excretion increased 4 days after the initiation of HDTB and remained elevated thereafter (pre-HDTB = 82.2 +/- 2.4/total volume; mid- to late HDTB = 89.4 +/- 2.1; p = .02). Plasma renin activity increased significantly with HDTB (pre-HDTB = 1.28 +/- 0.21 ng/mL/h; end HDTB = 1.69 +/- 0.18; p = .01), but serum aldosterone did not change. A significant decrease in autonomic responsiveness and an increase in leg compliance were observed. CONCLUSIONS: We conclude that even in the presence of a high-average salt intake diet, simulated microgravity leads to renal, cardioendocrine, and cardiovascular system alterations that likely contribute to cardiovascular deconditioning.

Adult↗

Orthostatic stress by lower body negative pressure and its body fluid distribution kinetics under microgravity.

To support the hypothesis that interstitial fluid loss is one of the components of the "cardiovascular deconditioning" induced by space flight, a series of three experiments was performed in one subject, after 5 days in space: 1) standard thigh cuffs were inflated up to suprasystolic pressure values (CUFF I) for two minutes, 2) Half an hour later a lower body negative pressure test (LBNP) followed with -15 mmHg for 15, -30 mmHg for 5, and -40 mmHg for 15 minutes, 3) Twenty minutes after that, the CUFF maneuver was repeated (CUFF II). Body fluid shifts were detected by quadripole segmental electrical impedance (BIM) and by electrical impedance tomography (APT). The APT electrodes were placed directly under one of the thigh cuffs. Cardiovascular reaction patterns were observed by continuous ECG-recordings and by minute-by-minute arm cuff blood pressure measurements. By means of segmental impedance the expected body fluid change in the abdominal, thigh, and calf regions could be detected. The thoracic segment showed no significant changes in microgravity. However, the calf increased its electrical impedance roughly by 50%. The interstitial fluid in the skin and musculature, detected by APT during CUFF I, was reduced more than 50%. The LBNP-maneuver was able to refill this interstitial space. However, only the higher levels (LBNP > 15 mmHg) showed the outward filtration component during the constant LBNP levels. In addition, the LBNP-experiment clearly showed the reduced ability to cope with orthostatic stress. Pulse pressure dropped and heart rate increased much more than on ground. The fluid displacement during CUFF I showed a similar hemodynamic response, which had not been seen on ground before. The CUFF II maneuver after LBNP showed that the reaction had returned to normal. This leads to the conclusions that LBNP can counteract cardiovascular deconditioning, but only higher LBNP-levels are able to transfer fluid into the interstitial spaces of the legs, if they are emptied by the loss of gravitational forces.

Aerospace Medicine↗

[Functional state of the cardiovascular system system during combined exposure to 28-day immersion, rotation in a short radius centrifuge, and physical loading on a bicycle ergometer].

The cardiovascular function of four test subjects exposed to 28-day "dry" immersion was examined before and after 6-day cycles of rotation in a short-arm centrifuge to provide 1-2 Gz, bicycle ergometer exercise, and their combination. An exposure to acceleration of 3 Gz in a 7.25 m arm centrifuge was used as a provocative test. The above countermeasures reduced but not eliminated entirely immersion-induced cardiovascular deconditioning. From this study a combined use of acceleration of 1-2 Gz in a short-arm centrifuge and bicycle ergometer exercise can be recommended as a countermeasure against cardiovascular deconditioning in weightlessness.

Blood Pressure↗

Effects of graded load of artificial gravity on cardiovascular functions in humans.

An artificial gravity and ergometric exercise loading device for human use was manufactured. It has the capacity of a max 2 G-load at the heart level, and a max 150 W of work-load. Eight subjects (six completed) were subjected to four repeated trials with or without 20 W ergometric exercise. Anti-G score, defined as the G-load x running time to the endpoint, was significantly higher in the exercise trials than standing trials. Heart rate (HR), mean arterial pressure (MAP), thoracic fluid index (TFI) were significantly superior during the exercise trials. Artificial gravity by centrifuge at 1.2 or 1.4 G with 40 or 60 W of ergometric workload may be an excellent countermeasure against cardiovascular deconditioning after long exposure to microgravity.

Adult↗

Orthostatic tests after a 4-day confinement or simulated weightlessness.

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6 degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower-body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D-1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT and LBNP without difference between D-1 and R1. This experiment showed that a 4-day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.

Adult↗

Norepinephrine kinetics in the rat with tail-suspension-induced central hypervolemia, as a model of cardio-vascular deconditioning.

Tail-suspension (TS) in the rat represents an interesting experimental condition to mimic, on Earth, the microgravity-induced cardiovascular deconditioning although the rat's profile of response is partially different from human's. To investigate underlying pathophysiological mechanisms, we have speculated on a decreased activity of the sympathetic system, (sigma S) triggered by the increase of the central venous pressure (CVP) induced by TS. Thus a decreased activity of the sigma S could account, at least partly, for the deconditioning of the cardiovascular system. The sympathetic activity (sigma A) was evaluated through measurement of the norepinephrine (NE) kinetics in rats that were tail-suspended for either 6, 24 or 48 hours. Neither NE spillover rate nor metabolic clearance rate were changed during TS, as compared to control. Thus, TS for a short period of time in the rat is unlikely to trigger a decrease of the sigma A.

Animals↗

Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats.

To verify whether a long-term weightlessness simulation was associated with development of cardiovascular deconditioning, male Wistar rats were tail suspended for 13 days and then removed for a 24-h recovery. Blood pressure (BP) and heart rate (HR) responses, their spectral properties, and the pharmacologically tested baroreceptor reflex sensitivity were studied throughout the suspension period and after removal from the tail suspension device. BP, HR, and their variability were not altered over the experimental period, and there were no indications of orthostatic intolerance on release from head-down suspension. Spectral properties of BP and HR were unchanged during the experiment, and tail suspension did not induce modifications in the baroreceptor reflex sensitivity. These results taken together suggest that cardiovascular deconditioning may not be developed even after long-term hindlimb suspension in rats, in contrast to humans exposed to actual or simulated weightlessness. Our results raise issue with the use of tail-suspended rats as a valid model for the study of alterations in cardiovascular function induced by spaceflight in humans.

Animals↗

Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb-unloaded rats.

Prolonged exposure to microgravity or bed rest produces cardiovascular deconditioning, which is characterized by reductions in plasma volume, alterations in autonomic function, and a predisposition toward orthostatic intolerance. Although the precise mechanisms have not been fully elucidated, it is possible that augmented cardiopulmonary reflexes contribute to some of these effects. The purpose of the present study was to test the hypothesis that sympathoinhibitory responses to volume expansion are enhanced in the hindlimb-unloaded (HU) rat, a model of cardiovascular deconditioning. Mean arterial blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) responses to isotonic volume expansion (0.9% saline iv, 15% of plasma volume over 5 min) were examined in conscious HU (14 days) and control animals. Volume expansion produced decreases in RSNA in both groups; however, this effect was significantly greater in HU rats (-46 +/- 7 vs. -25 +/- 4% in controls). Animals instrumented for central venous pressure (CVP) did not exhibit differences in CVP responses to volume expansion. These data suggest that enhanced cardiopulmonary reflexes may be involved in the maintenance of reduced plasma volume and contribute to attenuated baroreflex-mediated sympathoexcitation after spaceflight or bed rest.

Animals↗

Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats.

Cardiovascular deconditioning occurs in astronauts after spaceflight or in individuals subjected to bed rest. It is characterized by an increased incidence of orthostatic intolerance. The mechanisms responsible for orthostatic intolerance are likely multifactorial and may include hypovolemia, autonomic dysfunction, and vascular and cardiac alterations. The arterial baroreflex is an important compensatory mechanism in the response to an orthostatic stress. In a previous study, we demonstrated that arterial baroreflex mediated sympathoexcitation was blunted in hindlimb-unloaded (HU) rats, a model of cardiovascular deconditioning. The arterial baroreflex also contributes to the regulation of vasoactive hormones including vasopressin and angiotensin II. In the present study, we tested the hypothesis that the neurohumoral response to hypotension is also attenuated in rats after 14 days of hindlimb unloading. To test this hypothesis, the vasodilator diazoxide (15 or 25 mg/kg) or saline (0.9%) was administered to produce hypotension or control conditions, respectively, in conscious HU and control rats. Plasma samples were collected and assayed for vasopressin and plasma renin activity (PRA). Diazoxide (25 mg/kg) produced significant increases in vasopressin and PRA compared with saline controls. HU rats exhibited significantly higher levels of vasopressin at rest and the increase in vasopressin levels during hypotension was enhanced by hindlimb unloading. Neither resting nor hypotension-induced PRA was altered by hindlimb unloading. These data suggest that although baroreflex-mediated sympathoexcitation is blunted by hindlimb unloading, hypotension-induced vasopressin release is enhanced and hypotension-induced PRA is unaffected. Increased circulating vasopressin may serve to compensate for blunted baroreflex regulation of sympathetic nervous activity produced by hindlimb unloading or may actually contribute to it.

Animals↗

Comparison of a 4-day confinement and head-down tilt on endocrine response and cardiovascular variability in humans.

The aim of this study was to determine the effects of a 4-day head-down tilt (HDT; -6 degrees) and 4-day confinement on several indicators that might reflect a state of cardiovascular deconditioning on eight male subjects. Measurements were made of endocrine responses, heart rate variability and spontaneous baroreflex response (SBR) slope before, during and after each intervention. Plasma volume decreased by 10 percent after the 4-day HDT. The concentration of active renin was increased and that of urinary atrial natriuretic peptide decreased during the 4-day experiment in both groups. Plasma arginine vasopressin concentration decreased significantly only after 4-day confinement. After the 4-day HDT, one of the spectrum analysis parameters was statistically changed: the parasympathetic indicator decreased significantly (P <0.05) whereas the sympathetic indicator and the total power spectrum were unaltered. After 4-day confinement spectrum analysis parameters were not statistically altered. A significant decrease of SBR (P <0.05) was noticed only after the 4-day HDT. These data would suggest that exposure to a 4-day HDT was sufficient to induce a cardiovascular deconditioning which may have been induced by confinement and inactivity.

Adult↗

The venous tone is not altered after three-week tail suspension in rats.

Cardiovascular deconditioning observed in humans during spaceflight has been suggested to be related in part to changes in venous compliance, mechanisms including skeletal muscle deconditioning. However, increased venous compliance was observed during very short term simulations (24 to 48 hours), and during an over 28-day simulation the hyperdistensibility tended to decrease whereas the muscular changes were still present (2). In the first case, muscular changes can not explain the venous alterations because of the short delay. In the second case, the relationship between muscular and venous alterations disappeared. Finally, it is suggested that factors other than muscular ones could explain the changes in venous compliance observed during spaceflights. The fact that orthostatic hypotension has never been observed after hindlimb suspension in the rat raises issue with the use of tail-suspended rats as a valid model for the study of the mechanisms involved in cardiovascular deconditioning induced by spaceflight in humans. However, in vitro altered responsiveness of the vena cava to norepinephrine were observed in rat after spaceflight and tail suspension. The purpose of the experiments was to verify if any change occurs in venous tone measured in vivo in rats after three-week tail suspension.

Animals↗

Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure.

To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.

Animals↗

Artificial gravity in Space: vestibular tolerance assessed by human centrifuge spinning on Earth.

Artificial gravity created by the astronauts themselves, without any external power supply, by pedalling on coupled counterrotating bicycles along the inner wall of the space module (Twin Bikes System, TBS), was previously suggested (Antonutto et al., 1991) to prevent musculo-skeletal decay and cardiovascular deconditioning during long term space flights. To investigate whether this unusual rotating environment would determine abnormal stimulations of the vestibular system due to Coriolis cross coupled accelerations, thus leading to acute motion sickness (AMS), the conditions of a rotating environment were reproduced in a human centrifuge. A cycloergometer was fixed to the arm of the centrifuge, the rotation speed of which was equal to that yielding 1 g at the feet level in the TBS (i.e. ranging from 19 to 21 RPM). The ergometer position was such that the combination of the horizontal and gravitational acceleration vectors was 1.414 at the inner ear level and was aligned along the head to feet axis. Three subjects, pedalling at 50 W on a cycloergometer during centrifuge's spinning, were asked to move the head following an AMS' provocation protocol. None of them developed any AMS symptoms. This supports the look of the TBS as tool for avoiding musculo-skeletal and cardiovascular deconditioning during long term space flights.

Adult↗

Effect of 28-day head-down bed rest with countermeasures on heart rate variability during LBNP.

The effect of exercise and LBNP countermeasures on the cardiovascular deconditioning response have been evaluated by the study of heart rate variability during progressive LBNP tests before, during (day 15), and after 28 d continuous 6 degrees head-down tilt bed rest. Twelve healthy men (age 27-42 years) were studied in two groups. Six were assigned to a countermeasure regime (CM) consisting of strenuous short-term resistance exercise once per day, 6 days per week from day 7 to day 28, combined with lower body negative pressure (LBNP, -28 mm Hg) for 15 min on days 16, 18, 20, and 22-28. Results were compared with data from six subjects, matched on the basis of maximum oxygen uptake, who received no countermeasures (No-CM). The main effects of bed rest were seen in reductions in RR-interval, and in total spectral power. The results of spectral analysis showed a significant reduction in an index of parasympathetic activity with a nonsignificant increase in a sympathetic indicator. The fractal component of heart rate variability was reduced also, suggesting a change in cardiovascular control mechanisms. Although there were significant differences between CM and No-CM for a number of variables, there were no bed rest by countermeasure interaction effects in the statistical analysis. These results suggested that this particular series of countermeasures was ineffective in preventing at least certain changes indicative of cardiovascular deconditioning with 28 d head-down tilt bed rest.

Adult↗

Does the chronic fatigue syndrome involve the autonomic nervous system?

PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and predisposition to neurally mediated syncope reported in this patient group. PATIENTS AND METHODS: Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and premorbid and coexisting psychiatric disorders. The relationship between autonomic test results, cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic neuropathy was explored. RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01) and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P < 0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function (systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P < 0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twenty-five percent of CFS subjects had a positive tilt table test. The physical activity index was a significant predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy. CONCLUSION: Patients with CFS show alterations in measures of sympathetic and parasympathetic nervous system function. These results, which provide the physiological basis for the orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.

Adult↗

Does resistance exercise prevent body fluid changes after a 90-day bed rest?

Although various exercise regimens are commonly used as countermeasures to reduce the cardiovascular deconditioning induced by microgravity, the underlying mechanisms are not well understood. In this study we aimed to test whether lower limb resistance exercise with flywheel technology can prevent the fluid homeostasis alterations induced by 90-day head-down tilt bed-rest (HDT), and thus improve orthostatic tolerance. Total body water (TBW, measured by isotope dilution) and plasma volume (PV, calculated from the haemoglobin and the haematocrit) were measured in a control group (Co, n=9) and a countermeasure group (CM, n=9). Simultaneously, plasma atrial natriuretic peptide (ANP), renin (AR), and aldosterone (Aldo), as well as urinary anti-diuretic hormone (ADH), were measured. Orthostatic tolerance was evaluated with a 10 min +80 degrees tilt-test the first day of recovery. After HDT, both groups showed a comparable decrease in orthostatic tolerance [8.2 (0.9) min, Co; 8.0 (0.7) min, CM], PV [-4.7 (1.8)%, Co; -6.2 (2.5)%, CM, P<0.05] and TBW [-6.3 (5.4)%, Co; -3.7 (2.1)%, CM, P<0.05]. AR [97.4 (22.0)%, Co; 117.3 (26.4)%, CM] and Aldo [111.3 (58.4)%, Co; 100.6 (52.0)%, CM] increased significantly in both groups but the countermeasures produced no noticeable effects [data are expressed as mean (SE)]. The drop in ANP was also similar in both groups [-42.0 (15.2)%, Co; -51.1 (27.7)% for the CM]. Surprisingly, urinary ADH declined similarly in both groups during the basal data control period [-25.3 (5.2)%, Co; -26.1 (9.6)%, CM) and was sustained at this level during the 90-day HDT. These results show that, under the conditions described, the flywheel exercise device failed to improve characteristic manifestations of cardiovascular deconditioning and suggest that more frequent and powerful exercise, associated with another device (e.g. LBNP) might be a better countermeasure.

Adult↗