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Hemodynamic Studies of the Legs Under Weightlessness
... The leg volume changes occur in two phases, an initial rapid decrease and a slower component that occurs over the course of the mission (48,60). The abrupt nature of the initial volume decrease can only be due a translocation of fluids, while the slower component is probably due to extravascular fluid loss and muscle atrophy (36,60,72). HDT. ...
... Skylab data suggest that blood flow to the legs is actually increased in microgravity (72). Thornton et al. (72) propose that the increase in leg blood flow may be secondary to the increased cardiac output observed in microgravity. ...
... Of these changes, the in-flight decrease in CVP was a surprise to many researchers (7). It was first hypothesized that the fluid shift-induced increase in central blood volume would cause a subsequent increase in CVP (72). Catheterization data from three subjects clearly show a decrease in CVP which Buckey et al. (7) suggest may be due to a combination of relaxation of the venous smooth muscle and a decrease in blood volume. ...
This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity.
There were 10 healthy male subjects who were exposed to a 2-h tilt protocol which started in the standing position, and was followed by 30 min supine, 30 min standing, 30 min supine, 30 min of -12 degrees head down tilt (HDT, to simulate microgravity), 15 min of HDT with venoconstrictive thigh cuffs inflated, a further 10 min of HDT, 5 min supine, and 10 min standing. To increase the sensitivity of the techniques in an Earth-based model, 12 degrees HDT was used to simulate microgravity effects on body fluid shifts. Volume changes were measured with anthropometric sleeve plethysmography.
Transition to the various tilt positions resulted in concomitant decrements in leg volume (Stand [STD] to Supine [SUP], -3.0%; SUP to HDT, -2.0%). Inflation of the venoconstrictive thigh cuffs to 50 mmHg, during simulated microgravity, resulted in a significant 3.0% increase in leg volume from that seen in HDT (p < 0.01). No significant changes in systemic cardiovascular parameters were noted during cuff inflation.
We conclude that venoconstrictive thigh cuffs, inflated to 50 mmHg for 15 min during 12 degrees HDT, can create a more Earth-like fluid distribution. Cuffs could potentially be used to ameliorate the symptoms of cephalad edema seen with space adaptation syndrome and to potentiate existing fluid volume countermeasure protocols.
... Orthostatic challenge data was tabulated and the volume of peripheral fluid shifts were calculated for: (i) venous cuff occlusion (VCO) during spaceflight (Thornton & Hoffler, 1974); (ii) sit-to-stand (STS) tests (Frey et al., 1994); (iii) head-up tilt (HUT) tests (Laszlo et al., 2001); (iv) lower-body negative pressure (LBNP) (Lundvall et al., 1993); ...
... (v) short-arm human centrifugation (SAHC) (Iwase, 2005); and (vi) VCO on Earth in the present study (Table 3.3). Thornton and Hoffler (1974) Frey et al. ...
Spaceflight induces physiological deconditioning, despite extensive exercise countermeasures. Furthermore, post-flight orthostatic intolerance (OI) and visual impairment and intracranial pressure (VIIP) syndrome; possibly related to venous congestion (VC) suggest more holistic countermeasures, such as artificial gravity (AG) short-arm human centrifugation (SAHC) are warranted. SAHC may reduce OI and VIIP incidence through headward fluid shift/pressure reversal; and thus beneficial effects on cerebral hemodynamics. Therefore, this thesis examined how peripheral fluid shifts, induced by various orthostatic challenges, affect central, peripheral, and cerebral hemodynamics, including indices of VC, in healthy participants. Study one induced 5 min bilateral lower-limb venous cuff occlusion (VCO) up to 120mmHg in nine participants. VCO produced significant increments in leg volume (41-158mL;p<0.05); however, HR and cerebral tissue oxygenation (cTSI) were unchanged, suggesting an inadequate orthostatic challenge. Study two involved twenty participants experiencing 10 min SAHC to 2.4+Gz footlevel with increased g-gradients; specifically, moving rotational axis Position (RAP), independent of g-level, towards the body. Increasing SAHC g-gradients reduced the HR response and increased g-tolerance (χ2(1, n=20)=8.57;p=0.003), similar to decreasing g-level. Heart-level-RAP did not improve cTSI as hypothesised, possibly due to VC. Thus, study three used 5 min head-down tilt (HDT) to -24° and -40mmHg lower body negative pressure (LBNP) on sixteen participants to evaluate VC during headward fluid shifts HDT induced significant VC below -12° p<0.05), abolished with -40mmHg LBNP (107±11 vs. 1±5mm2;p<0.05), and increased cerebral blood flow when LBNP-peripheral and HDT-headward fluid shifts balanced (-0.71±0.56 vs. 4.12±1.36cm.s-1;p=0.013). This thesis suggests that VCO is a poor model of ravitational fluid shifting but large g-gradient SAHC, via heart-level-RAP, is effective; and crucially, more tolerable at higher g-levels. VC may play an important role in crogravity fluid shift related OI and VIIP, which -6° bed rest studies fail to induce. Thus, AG with optimal RAP and VC amelioration, may be a tolerable and effective spaceflight countermeasure.
... IT HAS BEEN SHOWN, during both spaceflights and ground simulation studies, that leg venous hemodynamics was greatly modified under the effects of prolonged microgravity (2,3,5,9,10,18). These changes are part of the cardiovascular deconditioning syndrome and are probably one of the main causes of the orthostatic intolerance exhibited by a great number of astronauts when they return to Earth (13). ...
... Ground simulation models, at least those designed for the study of changes in leg venous hemodynamics, have usually been utilized for periods of observation not exceeding 1 mo. In some of these studies, the increase in venous compliance or distensibility tended to lessen between the third and the fifth week of bed rest (9,10,18). The question is then whether a new state of equilibrium may be established in the venous system during the second month of simulated microgravity exposure and what the nature of this new state of equilibrium may be. ...
... Hemodynamic mechanisms Hypovolemia [39, 218, 229, 230] Increased venous capacitance [231, 232] Reduced cardiac performance [41, 42, 233, 234] Autonomic mechanisms Sympatho-adrenal dysfunction [51, 235, 236] Non-cardiovascular mechanisms Reduced exercise capacity [237] Neuro-vestibular plasticity [47, 238] 15 % decrease in red cell volume. Leach reported a reduction in plasma volume of 4 % for the three Apollo 17 astronauts [218]; landing day red cell volumes were variably reduced between 2 % and 10 % during the Apollo program [219]. ...
... During the Skylab 4 mission, changes in the distensibility of the leg veins were determined using in-flight venous occlusion plethysmography. The results suggest that early in flight, venous leg volume is significantly increased for a given occlusion pressure [231]. These results are difficult to interpret in terms of changes of the capacitive properties of the leg veins. ...
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2004. Includes bibliographical references (p. 163-185). The cardiovascular response to changes in posture has been the focus of numerous investigations in the past. Yet despite considerable, targeted experimental effort, the mechanisms underlying orthostatic intolerance (OI) following spaceflight remain elusive. The number of hypotheses still under consideration and the lack of a single unifying theory of the pathophysiology of spaceflight-induced OI testify to the difficulty of the problem. In this investigation, we developed and validated a comprehensives lumped-parameter model of the cardiovascular system and its short-term homeostatic control mechanisms with the particular aim of simulating the short-term, transient hemodynamic response to gravitational stress. Our effort to combine model building with model analysis led us to conduct extensive sensitivity analyses and investigate inverse modeling methods to estimate physiological parameters from transient hemodynamic data. Based on current hypotheses, we simulated the system-level hemodynamic effects of changes in parameters that have been implicated in the orthostatic intolerance phenomenon. Our simulations indicate that changes in total blood volume have the biggest detrimental impact on blood pressure homeostasis in the head-up posture. If the baseline volume status is borderline hypovolemic, changes in other parameters can significantly impact the cardiovascular system's ability to maintain mean arterial pressure constant. In particular, any deleterious changes in the venous tone feedback impairs blood pressure homeostasis significantly. This result has important implications as it suggests that al-adrenergic agonists might help alleviate the orthostatic syndrome seen post-spaceflight. by Thomas Heldt. Ph.D.
... IT HAS BEEN SHOWN, during both spaceflights and ground simulation studies, that leg venous hemodynamics was greatly modified under the effects of prolonged microgravity (2,3,5,9,10,18). These changes are part of the cardiovascular deconditioning syndrome and are probably one of the main causes of the orthostatic intolerance exhibited by a great number of astronauts when they return to Earth (13). ...
... Ground simulation models, at least those designed for the study of changes in leg venous hemodynamics, have usually been utilized for periods of observation not exceeding 1 mo. In some of these studies, the increase in venous compliance or distensibility tended to lessen between the third and the fifth week of bed rest (9,10,18). The question is then whether a new state of equilibrium may be established in the venous system during the second month of simulated microgravity exposure and what the nature of this new state of equilibrium may be. ...
Leg venous hemodynamics [venous distensibility index (VDI), arterial flow index (AFI), half-emptying time (T1/2)], and leg volumes (LV) were assessed by mercury strain-gauge plethysmography with venous occlusion and volometry, respectively, in seven men before, during, and after 42 days of 6 degrees head-down bed rest. Results showed a high increase in VDI up to day 26 of bed rest (+50% vs. control at day 26, P < 0.05), which tended to subside thereafter (+20% increase vs. control value at day 41, P < 0.05). VDI changes were associated with parallel changes in T1/2 (+54% vs. control at day 26 of bed rest, P < 0.05, and +25% vs. control at day 41, P < 0.05) and with a decrease in AFI (-49% at day 41 vs. P < 0.05). LV continuously decreased throughout bed rest (-13% vs. control at day 41, P < 0.05) but was correlated with VDI only during the first month of bed rest. These results show that during long-term 6 degrees head-down bed rest alterations of leg venous compliance are associated with impairment of venous emptying capacities and arterial flow. Changes in skeletal muscle mass and fluid shifts may account for venous changes during the first month of bed rest but, subsequently, other physiological factors, to be determined, may also be involved in leg venous hemodynamic alterations.
... MOST OF THE CARDIOVASCULAR changes induced by actual or simulated weightlessness are now considered to happen within the first days and seem to lead to a new and stable hemodynamic equilibrium after some days and at least for some months. The adaptation to actual 0 g can be characterized by a decrease in the volemia (7,11,15,16,28,31), perturbation of the baroreflex (21,25), decrease in the peripheral arterial vasoconstriction (7,12,40), and modification of the lower limb vein distensibility (40). During head-down-tilt (HDT) studies, similar changes were found for the volemia (20,26,29,34), baroreflex sensitivity (18), and peripheral arterial vasoconstriction (7,22), but of weaker amplitude. ...
... MOST OF THE CARDIOVASCULAR changes induced by actual or simulated weightlessness are now considered to happen within the first days and seem to lead to a new and stable hemodynamic equilibrium after some days and at least for some months. The adaptation to actual 0 g can be characterized by a decrease in the volemia (7,11,15,16,28,31), perturbation of the baroreflex (21,25), decrease in the peripheral arterial vasoconstriction (7,12,40), and modification of the lower limb vein distensibility (40). During head-down-tilt (HDT) studies, similar changes were found for the volemia (20,26,29,34), baroreflex sensitivity (18), and peripheral arterial vasoconstriction (7,22), but of weaker amplitude. ...
Thigh cuffs, presently named "bracelets," consist of two straps fixed to the upper part of each thigh, applying a pressure of 30 mmHg. The objective was to evaluate the cardiac, arterial, and venous changes in a group of subjects in head-down tilt (HDT) for 7 days by using thigh cuffs during the daytime, and in a control group not using cuffs. The cardiovascular parameters were measured by echography and Doppler. Seven days in HDT reduced stroke volume in both groups (-10%; P < 0.05). Lower limb vascular resistance decreased more in the cuff group than in the control group (-29 vs. -4%; P < 0.05). Cerebral resistance increased in the control group only (+6%; P < 0.05). The jugular vein increased (+45%; P < 0.05) and femoral and popliteal veins decreased in cross-sectional area in both groups (-45 and -8%, respectively; P < 0.05). Carotid diameter tended to decrease (-5%; not significant) in both groups. Heart rate, blood pressure, cardiac output, and total resistance did not change significantly. After 8 h with thigh cuffs, the cardiac and arterial parameters had recovered their pre-HDT level except for blood pressure (+6%; P < 0.05). Jugular vein size decreased from the pre-HDT level (-21%; P < 0.05), and femoral and popliteal vein size increased (+110 and +136%, respectively; P < 0.05). The thigh cuffs had no effect on the development of orthostatic intolerance during the 7 days in HDT.
... For pre-and postflight measurements, subjects were supine with the left leg elevated ϳ15°and with the knee slightly bent. This positioning was employed because it is a standard method for calf blood flow measurement (48), it simulates the relatively emptied leg venous conditions seen in microgravity (26,39,41), it approximates the posture astronauts naturally assume at rest in microgravity (40), and it is comfortable. Subjects were supine for 20-30 min before data collection. ...
... The present findings support some literature results that indicate that leg vasoconstriction occurs during spaceflight (33,42,44). Other data, all from longer duration flight (Ͼ2 wk), indicate increased leg blood flow (or reduced leg vascular resistance) in chronic microgravity (2,39). We measured calf hemodynamics between 4 and 12 days in-flight. ...
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.
... Exposure to weightlessness is accompanied by profound changes in most physiological systems, including disturbances in the sensorimotor, skeletal, and muscular systems, and, first of all, changes in the cardiovascular system (LeBlanc et al., 2000;Eckberg, 2003). In space, weightlessness immediately induces an upward fluid shift (Thornton and Hoffler, 1977). This fluid shift initiates subsequent changes in the cardiovascular system, including changes in the arterial and venous hemodynamics and vascular tone (Gazenko, 1984;Norsk et al., 2015). ...
Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system.
Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring.
Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP).
Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.
... Exposure to microgravity induces a number of deleterious effects on humans including muscle atrophy, loss of bone mineral density and cardiorespiratory deconditioning including orthostatic intolerance (OI) (see Hargens & Richardson, 2009;Blaber et al. 2011;Goswami et al. 2012Goswami et al. , 2013Goswami, 2017). In addition to microgravity-induced unloading, there is a headward fluid shift away from the lower limbs following the loss of the hydrostatic pressure gradient (Thornton & Hoffler, 1977). Long-arm human centrifugation (LAHC) and high-performance aircraft g-exposure is associated with relatively dose-dependent effects of +Gz upon the cardiovascular system and g-tolerance. ...
Key points:
The aim of this study was to determine the effect of rotational axis position (RAP and thus g-gradient) during short-arm human centrifugation (SAHC) upon cardiovascular responses, cerebral perfusion and g-tolerance. In 10 male and 10 female participants, 10 min passive SAHC runs were performed with the RAP above the head (P1), at the apex of the head (P2), or at heart level (P3), with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. We hypothesized that movement of the RAP from above the head (the conventional position) towards the heart might reduce central hypovolaemia, limit cardiovascular responses, aid cerebral perfusion, and thus promote g-tolerance. Moving the RAP footward towards the heart decreased the cerebral tissue saturation index, calf circumference and heart rate responses to SAHC, thereby promoting g-tolerance. Our results also suggest that RAP, and thus g-gradient, warrants further investigation as it may support use as a holistic spaceflight countermeasure.
Abstract:
Artificial gravity (AG) through short-arm human centrifugation (SAHC) has been proposed as a holistic spaceflight countermeasure. Movement of the rotational axis position (RAP) from above the head towards the heart may reduce central hypovolaemia, aid cerebral perfusion, and thus promote g-tolerance. This study determined the effect of RAP upon cardiovascular responses, peripheral blood displacement (i.e. central hypovolaemia), cerebral perfusion and g-tolerance, and their inter-relationships. Twenty (10 male) healthy participants (26.2 ± 4.0 years) underwent nine (following a familiarization run) randomized 10 min passive SAHC runs with RAP set above the head (P1), at the apex of the head (P2), or at heart level (P3) with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. Cerebral tissue saturation index (cTSI, cerebral perfusion surrogate), calf circumference (CC, central hypovolaemia), heart rate (HR) and digital heart-level mean arterial blood pressure (MAP) were continuously recorded, in addition to incidence of pre-syncopal symptoms (PSS). ΔCC and ΔHR increases were attenuated from P1 to P3 (ΔCC: 5.46 ± 0.54 mm to 2.23 ± 0.42 mm; ΔHR: 50 ± 4 bpm to 8 ± 2 bpm, P < 0.05). In addition, ΔcTSI decrements were also attenuated (ΔcTSI: -2.85 ± 0.48% to -0.95 ± 0.34%, P < 0.05) and PSS incidence lower in P3 than P1 (P < 0.05). A positive linear relationship was observed between ΔCC and ΔHR with increasing +Gz, and a negative relationship between ΔCC and ΔcTSI, both independent of RAP. Our data suggest that movement of RAP towards the heart (reduced g-gradient), independent of foot-level Gz, leads to improved g-tolerance. Further investigations are required to assess the effect of differential baroreceptor feedback (i.e. aortic-carotid g-gradient).
... In space, weightlessness immediately induces an upward fluid shift with the puffy face/chicken leg syndrome (Thornton and Hoffler, 1977). The onboard infrared photographs of the Skylab 4 crew members showed relatively empty lower limb veins, while the head veins were always fully filled and expanded (Gibson, 1977). ...
Background
The most applicable human models of weightlessness are −6° head-down bed rest (HDBR) and head-out dry immersion (DI). A detailed experimental comparison of cardiovascular responses in both models has not yet been carried out, in spite of numerous studies having been performed in each of the models separately.Objectives
We compared changes in central hemodynamics, autonomic regulation, plasma volume, and water balance induced by −6° HDBR and DI.Methods
Eleven subjects participated in a 21-day HDBR and 12 subjects in a 3-day DI. During exposure, measurements of the water balance, blood pressure, and heart rate were performed daily. Plasma volume evolution was assessed by the Dill–Costill method. In order to assess orthostatic tolerance time (OTT), central hemodynamic responses to orthostatic stimuli, and autonomous regulation, the 80° lower body negative pressure–tilt test was conducted before and right after both exposures.ResultsFor most of the studied parameters, the changes were co-directional, although they differed in their extent. The changes in systolic blood pressure and total peripheral resistance after HDBR were more pronounced than those after DI. The OTT was decreased in both groups: to 14.2 ± 3.1 min (vs. 27.9 ± 2.5 min before exposure) in the group of 21-day HDBR and to 8.7 ± 2.1 min (vs. 27.7 ± 1.2 min before exposure) in the group of 3-day DI.Conclusions
In general, cardiovascular changes during the 21-day HDBR and 3-day DI were co-directional. In some cases, changes in the parameters after 3-day DI exceeded changes after the 21-day HDBR, while in other cases the opposite was true. Significantly stronger effects of DI on cardiovascular function may be due to hypovolemia and support unloading (supportlessness).
... During spaceflight, weightlessness immediately induces a shift of blood and fluids from the lower segments of the body to the upper body, inducing puffy faces, as well as what has been termed chicken legs (Thornton & Hoffler, 1977). Approximately 2 litres of fluid are shifted upwards from the legs and, simultaneously, cardiac output is increased by 18-26% (Prisk et al. 1993;Shykoff et al. 1996;Norsk et al. 2006). ...
Key points:
Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure.It is unclear whether these changes persist throughout months of flight.Here, we show that cardiac output and stroke volume increase by 35–41% between 3 and 6 months on the International Space Station, which is more than during shorter flights.Twenty-four hour ambulatory brachial blood pressure is reduced by 8–10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space.It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station.
Abstract:
Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1–2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± se) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further.
... As space missions lengthen from weeks to years, the need for in-flight methods to monitor the muscle mass of astronauts becomes critical to health maintenance. In-flight measurements of muscle mass loss have been limited to anthropometric methods such as leg circumferences (28,30). However, these methods have a relatively poor sensitivity and can be affected by the fluid shifts that occur with adaptation to a microgravity environment (7). ...
This study validated bioelectrical impedance spectroscopy (BIS) with Cole-Cole modeled measurements of calf and arm segmental water volume and volume changes during 72 h of simulated microgravity and caloric restriction by using magnetic resonance imaging (MRI) muscle volume as a criterion method. MRI and BIS measurements of calf and upper arm segments were made in 18 healthy men and women [age, 29 +/- 8 (SD) yr; height, 171 +/- 11 cm; mass, 71 +/- 16 kg] before and after the intervention. Muscle volume of arm and leg segments by MRI was on average 15 +/- 10 and 14 +/- 8% lower, respectively, than the estimated total water volume by BIS (P < 0.01), but their correlations were excellent (r = 0.96 and r = 0.93, respectively). MRI- vs. BIS-predicted volume changes were a decrease of 49 +/- 68 vs. 41 +/- 62 ml in the calf and a decrease of 18 +/- 23 vs. 11 +/- 24 ml in the arm, respectively (P > 0.05 for both). BIS detected the extracellular water shifts in the calf resulting from the head-down tilt treatment, but the underfeeding protocol was not of sufficient duration or intensity to produce limb intracellular water changes detectable by BIS. BIS was highly correlated with segmental muscle volume and tracked changes associated with head-down tilt. Further research, however, is needed to determine whether BIS can accurately access separate changes in intracellular and extracellular volume.
Volume and distribution of intra and extra vascular fluid volume is the first and primary consideration of maintenance of human ability to function in an upright posture under gravitational and inertial loads, especially with static vertical posture in a gravitational field such as on Earth. It makes no difference whether a person working in a field has reduced total body fluid because of sweating all morning or an astronaut who has just returned to Earth from a week in orbit suddenly stands. If blood volume is too small to maintain an adequate cardiac filling pressure, both the worker and the astronaut are subject to the same laws of biophysics and may even experience syncope, a transient, self-limited loss of consciousness that is commonly referred to as ‘fainting’. Allowing individuals who have fainted to lay supine for a few minutes typically causes consciousness to return. Give them water over a brief time and the field worker can stand to eat his sandwich and drink his soda for lunch while the astronaut can walk out and wave to his admirers.
Long- and short-term exposure to microgravity significantly alters the cardiovascular system [1-9]. In this chapter, we describe the cardiovascular changes and the strategies used to manage problems in operational space medicine that arise as a consequence of those changes. Most descriptions of the effects of microgravity on the cardiovascular system have focused mainly on the physiological mechanisms that contribute to cardiovascular changes. Flight surgeons need to understand these important physiological effects on the human cardiovascular system so that they can place them within the operational context of a space mission. Crewmembers may also have subclinical cardiac abnormalities that could be exacerbated by the adaptive responses of the cardiovascular system to microgravity.
NASA
The article presents the current status of lower body negative pressure (LBNP) as a countermeasure for preventing orthostatic intolerance after space flight or bed rest. Devices discussed include the Chibis vacuum suit, the Anthrorack device, a collapsible device, and an inflatable device. Two bed rest studies examined the effect of LBNP and exercise on orthostatic tolerance; plasma volume; vasopressin, plasma renin activity, and catecholamines; and side effects.
The sections in this article are:
Seven healthy subjects were submitted to a 42-day head down bedrest, where leg venous compliance (venous distensibity index VDI) and leg volumes were assessed by mercury strain gauge plethysmography with venous occlusion and optoelectronic plethysmography, respectively. Plethysmographic and volometric measurements were made, before, during (at days 1, 4, 7, 14, 21, 26, 34 and 41), and after bedrest (days 1, 4, 7, 11 and 30 of the recovery period). Results showed a continuous decrease in leg volumes throughout bedrest, when VDI increased until day 26 of bedrest, and then decreased afterwards. The recovery period was characterized by a rapid return of VDI to prebedrest levels while leg volumes progressively normalised. These results showed that leg venous compliance changes are not always dependant upon skeletal muscle changes, and that factors other than size of muscle compartment are able to determine increases in leg venous compliance during long-term bedrest.
We quantified the impact of a 60-day head-down tilt bed rest (HDBR) with countermeasures on the arterial response to supine lower body negative pressure (LBNP). Twenty-four women [8 control (Con), 8 exercise + LBNP (Ex-LBNP), and 8 nutrition (Nut) subjects] were studied during LBNP (0 to -45 mmHg) before (pre) and on HDBR day 55 (HDBR-55). Left ventricle diastolic volume (LVDV) and mass, flow velocities in the middle cerebral artery (MCA flow) and femoral artery (femoral flow), portal vein cross-sectional area (portal flow), and lower limb resistance (femoral resistance index) were measured. Muscle sympathetic nerve activity (MSNA) was measured in the fibular nerve. Subjects were identified as finishers or nonfinishers of the 10-min post-HDBR tilt test. At HDBR-55, LVDV, mass, and portal flow were decreased from pre-HDBR (P < 0.05) in the Con and Nut groups only. During LBNP at HDBR-55, femoral and portal flow decreased less, whereas leg MSNA increased similarly, compared with pre-HDBR in the Con, Nut, and NF groups; 11 of 13 nonfinishers showed smaller LBNP-induced reductions in both femoral and portal flow (less vasoconstriction), whereas 10 of 11 finishers maintained vasoconstriction in either one or both regions. The relative distribution of blood flow in the cerebral versus portal and femoral beds during LBNP [MCA flow/(femoral + portal flow)] increased or reduced < 15% from pre-HDBR in 10 of 11 finishers but decreased > 15% from pre-HDBR in 11 of 13 nonfinishers. Abnormal vasoconstriction in both the portal and femoral vascular areas was associated with orthostatic intolerance. The vascular deconditioning was partially prevented by Ex-LBNP.
This chapter reviews the available medical observations, and discusses the possible mechanisms of adaptation of physiological systems to microgravity and their readaptation to earth's gravity after flight. An important mechanism of adaptation to changing environments is the formation of a functional system. The existence of a functional system or the formation of a new one is not sufficient for effective adaptation. Stable adaptation is achieved only when structural alterations develop in the cells and organs of the system, increasing its power to the level required by the environment. This is achieved by the formation of a structural track, which is the basis for long-term specific adaptation. The chapter also discusses immediate and long-term adaptation. Immediate adaptation includes activation and hyperfunction of existing functional systems or relatively rapid emergence of new and closely interrelated functional systems. Long-term adaptation is based on the formation of a systemic structural track that selectively increases the capacity of structures responsible for the control, ion transport, and energy supply in all organs and cells that constitute a single functional system responsible for adaptation.
Venous distensibility of the lower limbs was assessed in six healthy men who were submitted twice successively to 1 month of −6° head-down bedrest, with and without lower body negative pressure (LBNP) (LBNP subjects and control subjects, respectively). Venous capacity (Δ V
v,max, in ml·100 ml−1) of the legs was determined by mercury strain gauge plethysmography with venous occlusion. Plethysmographic measurements were made on each subject before (Dc), during (D6 and D20) and after (5th day of recovery, D+5) bedrest. During bedrest, LBNP was applied daily, several times a day to the subjects submitted to this procedure. Results showed a gradual increase in V
v,max (ml·100 ml−1) throughout the bedrest, both in the control group [Δ V
v,max = 2.11 SD 0.54 at Dc, 2.69 SD 0.29 at D6, 4.39 SD 2.08 at D20, 2.39 SD 0.69 at D+5, P<0.001 (ANOVA)] and in the LBNP group [Δ V
v,max = 2.07 SD 0.71 at Dc, 2.85 SD 1.19 at D6, 3.75 SD 1.74 at D20, 2.43 SD 0.94 at D+5, P<0.001 (ANOVA)], without significant LBNP effect. These increases were of the same order as those encountered during spaceflight. It is concluded that −6° head-down bedrest is a good model to simulate the haemodynamic changes induced by exposure to weightlessness and that LBNP did not seem to be a good technique to counteract the adverse effects of weightlessness on the capacitance vessels of the lower limbs. This latter conclusion raises the question of the role and magnitude of leg venous capacitance in venous return and cardiac regulation.
The causes of orthostatic intolerance following prolonged bed rest, head-down tilt or exposure to zero gravity are not completely understood. One possible contributing mechanism is increased venous compliance and peripheral venous pooling. The present study attempted to determine what proportion of the increased calf volume during progressive venous occlusion is due to deep venous filling. Deep veins in the leg have little sympathetic innervation and scant vascular smooth muscle, so their compliance may be determined primarily by the surrounding skeletal muscle. If deep veins make a large contribution to total leg venous compliance, then disuse-related changes in skeletal muscle mass and tone could increase leg compliance and lead to decreased orthostatic tolerance. The increase in deep venous volume during progressive venous occlusion at the knee was measured in 6 normal subjects using calf cross-sectional images obtained with magnetic resonance imaging. Conventional plethysmography was used simultaneously to give an independent second measurement of leg volume and monitor the time course of the volume changes. Most of the volume change at all occlusion levels (20, 40, 60, 80 and 100 mm Hg) could be attributed to deep venous filling (90.2% at 40 mm Hg and 50.6% at 100 mm Hg). It is concluded that a large fraction of the calf volume change during venous occlusion is attributable to filling of the deep venous spaces. This finding supports theories postulating an important role for physiological mechanisms controlling skeletal muscle tone during orthostatic stress.
Specific alterations in autonomic functions induced by endurance training may lead to a reduced ability to withstand orthostatic stress. This possibility has caused some authorities to suggest that, because of potentially greater pooling of blood in the lower extremities during gravitational loading, endurance-trained athletes may make poor astronauts. Although results from spaceflight studies have provided little evidence to support this suggestion, data from water-immersion studies indicate that endurance-trained athletes do become more orthostatically intolerant following a few hours of simulated weightlessness. Unfortunately, other evidence supporting the hypothesis that endurance training reduces orthostatic tolerance has not received adequate publication in the open scientific literature.
On the other hand, a number of studies which have been openly reported clearly refute this hypothesis. Nevertheless, the established physiological differences between endurance athletes and non-athletes are themselves sufficient to suggest that the hypothesis could be tenable. Consequently, it has to be concluded that the presently available information is both qualitatively and quantitatively inadequate to permit any definite statement regarding a possible relationship between aerobic power (V̇2max) and orthostatic tolerance.
After space-flights of less than ten days, orthostatic hypotension upon reentry is characterized by plasma volume depletion that may lead to activation of the Bezold-Jarisch reflex which is also considered to be the mechanism of vasovagal (neurocardiogenic) syncope. For space-flight of longer duration, loss of cardiovascular reflex control may take precedence over volume depletion and thus may have similarities to the orthostatic hypotension seen in patients with autonomic failure secondary to basal ganglial disease and peripheral neuropathies. Midodrine is an alpha-one agonist that produces arterial and venous constriction and leads to a decrease in heart rate by baroreceptor reflexes. The efficacy of Midodrine in successfully treating orthostatic hypotension secondary to autonomic failure has been shown in clinical trials. Midodrine's ability to vasoconstrict without increasing heart rate suggests that it might be a useful treatment for vasovagal syncope since stimulation of the Bezold-Jarisch reflex would be less likely. For post-space flight orthostatic hypotension, midodrine may be a useful adjunctive treatment to the measures currently being used.
Leg compression devices have been used extensively by patients to combat chronic venous insufficiency and by astronauts to counteract orthostatic intolerance following spaceflight. However, the effects of elastic and inelastic leggings on the calf muscle pump have not been compared. The purpose of this study was to compare in normal subjects the effects of elastic and inelastic compression on leg intramuscular pressure (IMP), an objective index of calf muscle pump function. IMP in soleus and tibialis anterior muscles was measured with transducer-tipped catheters. Surface compression between each legging and the skin was recorded with an air bladder. Subjects were studied under three conditions: (1) control (no legging), (2) elastic legging, and (3) inelastic legging. Pressure data were recorded for each condition during recumbency, sitting, standing, walking, and running. Elastic leggings applied significantly greater surface compression during recumbency (20 +/- 1 mm Hg, mean +/- SE) than inelastic leggings (13 +/- 2 mm Hg). During recumbency, elastic leggings produced significantly higher soleus IMP of 25 +/- 1 mm Hg and tibialis anterior IMP of 28 +/- 1 mm Hg compared to 17 +/- 1 mm Hg and 20 +/- 2 mm Hg, respectively, generated by inelastic leggings and 8 +/- 1 mm Hg and 11 +/- 1 mm Hg, respectively, without leggings. During sitting, walking, and running, however, peak IMPs generated in the muscular compartments by elastic and inelastic leggings were similar. Our results suggest that elastic leg compression applied over a long period in the recumbent posture may impede microcirculation and jeopardize tissue viability.(ABSTRACT TRUNCATED AT 250 WORDS)
Various factors may contribute to orthostatic intolerance (OI) observed after space flights or simulated weightlessness such as bed rest experiments: individual physical and physiological factors (arterial blood pressure (BP), height), physiological changes induced by real or simulated weightlessness (hypovolaemia, increase in venous distensibility), and space flight or simulation conditions (duration and counter-measure application). Our purpose was to test which of these factors were dominant in contributing to the OI. This was assessed in 47 healthy men participating in bed rest experiments of 4, 14, 28, 30 and 42 days, with or without counter-measures (medical stockings, lower-body negative pressure (LBNP), LBNP + muscular exercise). Nineteen subjects did not finish the orthostatic test (60 degrees head-up tilt or stand test) after bed rest. The occurrence of OI was associated with greater height, low resting BP, greater changes in resting lower-limb venous distensibility throughout the bed rest, and absence of counter-measures.
The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.
The cardiovascular function is one of the main disturbed by weightlessness: it is particularly affected by the astronaut's return to Earth, where symptoms linked to the cardiovascular deconditioning syndrom appear in the following forms: (1) orthostatic intolerance with its risk of syncope: (2) higher submaximal oxygen consumption for an equivalent work load. Lower Body Negative Pressure (LBNP) is intended to stimulate the venous system of the lower limbs; however, the specific effects of periodical LBNP sessions on the orthostatic intolerance have never been studied. With this objective in mind, 5 volunteers took part in two recent antiorthostatic bedrest experiments for 30 days. In the first experiment 3 subjects were submitted to several sessions of LBNP experiment per day and 2 others were controls; in the second experiment the LBNP group of the 1st one became controls and vice-versa. Two orthostatic investigations were performed: (1) 5 days before the bedrest; (2) at the end of the 30 day bedrest period. The results showed: (1) when the subjects were control, a high orthostatic intolerance post bedrest with 3 syncopes and one presyncopal state during the first minutes of the tilt test; (2) when the subjects were submitted to LBNP sessions, no orthostatic intolerance.
The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.
Exposure to lower body negative pressure (LBNP) with oral salt and water ingestion has been tested by astronauts as a countermeasure to prevent postflight orthostatic intolerance. Exercise is another countermeasure that astronauts commonly use during spaceflight to maintain musculoskeletal strength. We hypothesize that a novel combination of exercise and simultaneous exposure to lower body negative pressure during spaceflight will produce Earth-like musculoskeletal loads as well as cardiovascular stimuli to maintain adaptation to Earth's gravity. Results from recent studies indicate that leg exercise within a LBNP chamber against the suction force of 100 mmHg LBNP in horizontal-supine posture produces an equivalent, if not greater exercise stress compared to similar leg exercise in upright posture (without LBNP) against Earth's gravity. Therefore, the concept of LBNP combined with exercise may prove to be a low cost and low mass technique to stress the cardiovascular and the musculoskeletal systems simultaneously.
NASA
The authors present a physiological basis for the use of exercise as a weightlessness countermeasure, outline special considerations for the development of exercise countermeasures, review and evaluate exercise used during space flight, and provide new approaches and concepts for the implementation of novel exercise countermeasures for future space flight. The discussion of the physiological basis for countermeasures examines maximal oxygen uptake, blood volume, metabolic responses to work, muscle function, bone loss, and orthostatic instability. The discussion of considerations for exercise prescriptions during space flight includes operational considerations, type of exercise, fitness considerations, age and gender, and psychological considerations. The discussion of exercise currently used in space flight examines cycle ergometry, the treadmill, strength training devices, electrical stimulation, and the Penguin suit worn by Russian crews. New approaches to exercise countermeasures include twin bicycles, dynamic resistance exercisers, maximal exercise effects, grasim (gravity simulators), and the relationship between exercise and LBNP.
The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 degrees, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 hr. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin and aldosterone inhibition.
A significant fraction of astronauts experience postflight orthostatic intolerance (POI) during 10-min stand tests conducted on landing day. The average time that nonfinishers can stand is about 7 min. This phenomenon, including the delay in occurrence of presyncope, was studied with a five-compartment model of the cardiovascular system incorporating compartments for the heart/lungs, systemic arteries and cephalic, central, and caudal veins. The model included 28 independent parameters, including factors characterizing cardiac performance, vascular resistance, intrathoracic pressure, nonlinear venous compliance and circulating blood volume, and 13 dependent parameters, including cardiac output and cardiac and vascular compartment pressures and volumes. First, a sensitivity analysis of hemodynamic indicators of presyncope to independent parameters was performed. Results demonstrated that both cardiac output and arterial pressure were most sensitive to volume-related parameters, particularly total blood volume, and less sensitive to peripheral resistance. Next, a simulated postflight stand test confirmed that fluid loss due to capillary filtration, particularly from the caudal region where transmural pressure is high during standing, is a plausible mechanism of POI that also explains the delayed onset of symptoms in most astronauts. An accumulated drop in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a fluid loss of 280 mL. Finally, additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. It is therefore concluded that capillary filtration may play a key role in producing POI and that development of countermeasures should perhaps focus on reducing postflight capillary permeability or on stimulating volume-compensating mechanisms.
Hindlimb unweighting (HLU) in rats mimics the fluid shift experienced by astronauts and may serve as a model for ground-based orthostatic hypotension. It has been shown that the abdominal aorta of HLU rats exhibits a deficit in contractile response to adrenergic agonists. The hypothesis of the present study was that decreased activity in the RhoA/Rho-kinase pathway could contribute to that deficit. Wistar rats were subjected to 20 days of HLU treatment. Abdominal aorta rings from HLU and control rats were suspended in baths for measurement of contraction. Concentration response curves were obtained to the alpha adrenergic agonist, phenylephrine and the thromboxane-mimetic, U46619. HLU treatment caused decreased contraction in response to both. The Rho-kinase inhibitor, Y27632, caused a reduction in the phenylephrine-induced contraction in control, but not HLU aorta. Other rings were frozen after stimulation 1 microM U46619 or phenylephrine. Western analysis revealed a decreased expression of RhoA, but increased expression of both Rho kinase and MYPT1, the regulatory subunit of myosin light chain (MLC) phosphatase. MYPT1 and MLC phosphorylation was decreased by HLU in phenylephrine stimulated aorta. Decreased activity in the RhoA/Rho-kinase pathway may be involved in the decreased contraction seen in the HLU abdominal aorta.
The paper reviews the results of studies of changes undergone by several physiological systems (including the cardiovascular system, the fluid and electrolyte characteristics, the red blood cells, the bone and the muscle tissues, and the exercise capacity) due to the exposures to microgravity and to the adaptation to 1 G after a long-duration space flight. Special attention is given to the effects of various training protocols and countermeasures used to attenuate the physiological problems encountered upon return from space.
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