The mechanisms of cardiovascular adaptation to microgravity are triggered by the initial fluid shift from the lower to the upper part of the body (9,11,12,20). This fluid shift is known to induce a significant reduction of the circulating blood volume and a redistribution of the central and peripheral flows, which are more or less controlled by changes of the vascular resistance in the different vascular areas (2,4,7-10). The hypothesis of neurohormonal regulation of the volemia has been documented(10,11,17); however, few studies have been dedicated to the adaptation of the regional vascular areas.
During most short-term flights or HDT studies, a significant hypovolemia has been observed after some hours in real or simulated microgravity(20). Also, the cerebral flow was maintained and the vascular resistance reduced both at the cerebral and lower limb levels(4,7).
Presently, such patterns are not always so clearly observed, due to the use of various countermeasures such as LBNP, exercise, fluid loading and, more recently, “bracelets.” This last countermeasure is a recent Russian innovation that consists of small straps placed at the upper part of both thighs, applying a pressure of about 20 mm Hg. All of these countermeasures have a significant impact on the adaptation of the cardiovascular system to microgravity in addition to interfering with the development of orthostatic intolerance.
Several mechanisms are probably involved in orthostatic hypotension(16,19,25): reduced plasma volume, baroreflex changes, or increase in venous compliance, particularly of the lower limbs. Different tests allow the orthostatic tolerance and cardiovascular response to be assessed. The tilt test can be carried out according to different protocols of various duration (10-30 min). The stand test is often used after spaceflights. LBNP application, which causes pooling of blood in the lower extremities, can also be used to evaluate orthostatic tolerance and represents the only test usable inflight(14,20).
In each of our studies, performed either in real microgravity (Aragatz 25-d(4), Antares 14-d and Altair 21-d MIR spaceflights(6)), or in ground zero g simulations (28- and 30-d HDT), we used the same ultrasound methodology to assess cardiovascular hemodynamics (4,5). The main parameters of left heart function and of the peripheral arterial system (cerebral, carotid, renal, mesenteric, and femoral arteries) were measured at rest and during orthostatic tests (LBNP test or tilt test) several times pre, in, and postflight or HDT.
The first objective of our studies was to evaluate, by using echography and Doppler ultrasound, the cardiac and peripheral changes induced by exposure to 0 g during short-term flights without countermeasure(5), and during long-term flights according to the countermeasure used. The second objective was to assess the peripheral response to orthostatic test (tilt, stand, on 1 g, LBNP in 0g) in order to quantify the hemodynamic changes related to orthostatic intolerance. The third objective, as a consequence of the second, was to design one or several hemodynamic parameters that could predict the vascular response to orthostatic stress and highlight the efficiency of the different countermeasures.
MATERIALS AND METHODS
Arterial Doppler Parameters
The Doppler spectrum of any vessel supplying a low-resistance area shows a positive and important end-diastolic frequency (D) (Fig. 1, upper). The flow velocity, and thus end-frequency on the Doppler spectrum, never reaches the zero line. The ultrasound hemodynamic data(flow volume, mean frequency, and resistance) require either the use of both the image and the Doppler (duplex system), or can be obtained only from the Doppler velocity spectrum. For blood flow quantification(ml·min-1), we need to measure the vessel diameter, the angle between the Doppler beam and the vessel axis on the image, and the mean frequency on the Doppler spectrum. The vessel diameter is usually measured on an ultrasound image with a resolution of approximately 0.1-0.5 mm, depending on the device. An error of 0.3 mm on a vessel of 7-mm diameter(carotid/femoral arteries) will induce an error of 8.5% in area and in blood flow volume. Usually it is accepted that changes in blood flow volume lower than 10% are not significant. In order to evaluate the vascular resistance in different areas, high or low-resistance circulation, we used different Doppler resistance indices measured only on the Doppler frequency spectrum. For such parameters the error is less than 5%.
Low-resistance circulation: cerebral artery, renal artery, common carotid. The evaluation of vascular resistance in a limited area by Doppler is already validated and used in medicine (1,21). Various indices that measure the proportion of systolic flow within the mean forward flow (M) during one cardiac cycle, or the relative amplitude of systolic (S) to diastolic (D) flow have been proposed: Pulsatility Index =(S-D)/M (18), D/S ratio (21), Resistance Index = (S-D)/S (23), S/D ratio(24). Each of these indices, except one (D/S ratio), changes in proportion to the vascular resistance and in the same direction. As the resistance increases, the diastolic component decreases and the resistance indices increase. Nevertheless, these indices may be influenced by marked changes in heart rate or pulse blood pressure. Although these indices do not provide an absolute value of the vascular resistance, they change in proportion to the vascular resistance. A recent experiment carried out on animals (1) that consisted of measuring at the same time, and at the same level of the vessel, the blood flow (ml·mn-1), blood pressure (mm Hg) and the Doppler frequency parameters (no unit), has demonstrated a high correlation (r = 0.94) between the variations of the Doppler resistance indices and the actual variations of the vascular resistance (mm Hg·ml·mm-1). In our studies, we used the RI that changes from 0 to 1.
These indices are not angle-dependent, as they are ratios of frequencies measured on the same recording, that is to say, with the same angle. Therefore, in some cases, the vascular resistance can be monitored by using a Doppler sensor fixed in an adequate position at the level of the vessel of interest without visualizing the artery. The cerebral or carotid resistance changes are assessed by using skin sensors fixed on the skull (transcranial Doppler) or the neck.
High-resistance circulation: femoral artery. The Doppler frequency spectrum of any normal lower limb arteries shows a positive systolic frequency peak (S) followed by a negative frequency peak at the beginning of diastole (D) generated by the rebound of the systolic pressure wave from the arteriocapillary junction, which presents a high resistance to flow(Fig. 1, upper). Then, the reverse pressure wave rebounds on the aortic valves and creates a third positive frequency wave toward the extremity of the lower limbs. The amplitude of the reverse velocity, or frequency (D), depends on the amplitude of the distal vascular resistances when there is no major vascular lesion (stenosis) between the Doppler recording point (femoral, for example) and the distal vascular bed.
The vascular resistance in the area below the measuring point is evaluated by using the Doppler high-resistance index expressed as HRI = D/S, with S the systolic maximal forward-flow frequency and D the diastolic maximal reverse-flow frequency on the Doppler spectrum. This index was validated in an animal model (ewe) (3) by comparing the absolute values of lower limb HRI with those of the classic vascular resistances (Rv) calculated from the mean pressure and flow at the Doppler recording point (mm Hg·ml·min-1). The absolute values of each parameter showed a good correlation (r = 0.82) (Fig. 1,lower). This study confirms that the HRI values and variations are very representative of the vascular resistances. The HRI is not sensitive to heart rate variations. Finally, the HRI does not depend on the angle between the vessel and the Doppler beam, thus the evaluation of the resistance of the lower limb can be performed by using a simple continuous Doppler system fixed on the thigh, for example. Most of the time, the sensor is fixed in front of the superficial femoral artery because the HRI at that level represents the vascular resistance in the entire vascular bed below, that is to say, in the lower limb. Currently, the usefulness of the Doppler HRI has been demonstrated in the detection of orthostatic intolerance on subjects vascularly disadapted by a long exposure to 0 g or head-down tilt(5,6). The absence of femoral resistance increase during an orthostatic stress test, like lower body negative pressure, or tilt table, was associated with orthostatic intolerance signs.
Variation of hemodynamic parameter. In most experiments dedicated to the study of changes induced by 0 g, the subject is his own control. Therefore, as we compare the hemodynamic parameters with the same ones measured before the flight or the HDT, one may consider that some of the data used for the calculation of these parameters remain constant.
When measuring peripheral blood flow, one can consider that the carotid and the femoral artery diameters do not change significantly in microgravity. By this statement we eliminate the major factor of error in the determination of the blood flow volume. Therefore, the comparison between mean frequency (or velocity) pre and inflight (or HDT) becomes more representative of the actual blood flow volume variation than when using vessel diameter, which introduces a significant error. Another scenario frequently encountered is the assessment of Doppler hemodynamic data during orthostatic testing. For operational reasons, sensors are fixed on the skin and oriented toward the vessel of interest (cerebral, carotid, femoral arteries). Adapted harnesses have been designed to fix the sensors. In such conditions, the angle between the vessel and the Doppler beam remains constant, and any change of the maximum or mean frequency on the spectrum represents a change in blood flow volume. Vascular resistance can also be assessed by this system. Another advantage is that with an implanted skin sensor, all the Doppler parameters can be assessed and quantified in real time with high accuracy (less than 10% for blood flow, less than 5% for resistance index). Finally, blood flow volume changes are expressed in percentage of the preflight, pre-HDT, or pre-LBNP test values; thus, this information is much more accurate than the comparison of blood flow volume data calculated from the measured vessel diameter.
At rest. Cerebral, carotid, renal, mesenteric, and femoral hemodynamic parameters were monitored before, during, and after HDT or spaceflights using an ultrasound-Doppler system (conventional Duplex system 3.5 and 5 mHz or transcranial Doppler). ECG and blood pressure were measured at the same time.
Orthostatic tolerance test. Different tests are used to evaluate the orthostatic tolerance by measuring cardiovascular responses to those tests. The tilt test can be carried out according to different protocols, the subject being tilted from 0° to 70° during 10-30 min. The stand test is often used after spaceflights because it is easier to set up at the landing site. It consists of standing the subject by himself for some minutes(approximately 10 min). LBNP application induces a fluid shift from the cephalic part of the body toward the limbs. This transfer of liquid partially simulates the effect of hydrostatic pressure in a 1 g environment and induces an adaptive cardiovascular response. It represents the only test usable inflight and has the advantage of generating a progressive orthostatic stress (14,20).
The LBNP test for HDT studies consists of a 30-min rest period prior to LBNP (pre-LBNP or baseline), followed by a 3-min exposure to -20 mm Hg, -30 mm Hg, -40 mm Hg, and -50 mm Hg. The inflight test consists of two levels of depression -25 and -45 mm Hg of 10 min each. The LBNP test is interrupted whenever presyncopal symptoms and/or a blood pressure drop (drop of systolic blood pressure >25 mm Hg) occurred.
HDT and Flight Experiment Scenario
28-d HDT with and without LBNP countermeasures (CNES 1988-1989). Objective: Study of the cardiac and vascular changes induced by HDT at rest with and without LBNP countermeasure.
Twelve healthy volunteers participated in a 28-d HDT (-6°)(5). The experiment was approved by the French National Ethics Committee. The informed consent of the subjects was obtained, and the subjects were aware of their right to withdraw from the experiment at any time without any prejudice. In the control group, the six subjects stayed at rest during the 28 d of the HDT. In the countermeasure group, the six subjects were submitted to daily LBNP sessions during the entire HDT. The LBNP countermeasure session consisted of a 15-min LBNP at -30 mm Hg, once a day, every day.
By the end of the HDT period, each subject was submitted to a tilt table orthostatic tolerance test of 30 min. The test was interrupted as soon as the systolic pressure dropped by 20 mm Hg or more, or if presyncopal symptoms occurred. The subject was then considered as orthostatic intolerant.
The left ventricle function was assessed at rest by measuring the left ventricular volume, stroke volume, and cardiac output. However, the peripheral flow study consisted of measuring the carotid, renal, and femoral flows and resistances at rest and during LBNP. These parameters were measured pre-HDT, 1 h after the beginning of HDT, 1 wk, 2 wk, and 3 wk in HDT, the last day before the HDT ended, and 3 d post-HDT.
25-d Spaceflight without countermeasures (Aragatz 1988). Objective: Study of the cardiac and vascular adaptation to microgravity without LBNP.
During the 25-d French-Soviet spaceflight “Aragatz 1988”(4), one astronaut was investigated. The following vascular parameters were calculated: left ventricular volume, stroke volume and cardiac output, the cerebral and femoral flows and vascular resistances, and renal vascular resistance. The astronaut was not submitted to LBNP countermeasure sessions during the flight. Basal data were collected 60 and 3 d before the flight. Inflight, six cardiovascular sessions were performed: on flight days 4, 5, 15, 18, 20, and 24. Postflight measurements were taken on days +1, +3, +7.
30 d of HDT with and without LBNP+EXERCISE countermeasure (CNES 1990-1991). Objective: study of the influence of the LBNP countermeasure on the development of cardiovascular disadaptation.
Twelve healthy subjects participated to this second CNES long-term HDT(5). The six control subjects remained in HDT -6° position during 30 d without any countermeasures and without exercising. The six countermeasure subjects stayed in the same conditions as control only the 1st week. On week 2, they used exercise (isotonic and isometric) and were submitted to both exercise and LBNP during week 3 (LBNP one day to another) and week 4 (LBNP every day).
Both groups were submitted to orthostatic tolerance test pre-, in-, and post-HDT: pre-HDT, one tilt test (70°, 30 min long) and one LBNP (four steps of 3 min at -20, -30, -40, and -50 mm Hg). At HDT day 15 (before LBNP countermeasure) one LBNP test was the same as pre-HDT. At post-HDT day 1, one tilt test and one LBNP were the same as pre-HDT.
During LBNP, the cerebral and femoral blood flow volume and resistance changes were assessed by Doppler skin sensor. The flow distribution ratio(cerebral/femoral flow) was also measured.
Spaceflight of medium duration (Antares 14-d and Altair 21-d spaceflights) with and without countermeasures (thigh cuff“bracelets”) (1992/1993). Objective: Study the impact of the bracelets on the adaptation to microgravity(6).
These bracelets consist of two small straps fixed at the upper part of each thigh applying a maximum pressure of 20 mm Hg to the skin. This countermeasure is passive. The pressure of the thigh cuff partially reduces the venous return and probably the amplitude or the kinetics of the fluid shift at the beginning of the flight.
During the 14-d MIR-Antares flight (1992) (5) and 21-d MIR-Altair flight (1993) (6), we had the opportunity to investigate two cosmonauts; one using thigh cuffs from flight day 1-8 (14-d flight), the second without cuffs (21-d flight).
Renal, mesenteric, and splanchnic vascular resistances, cerebral and femoral flow volumes, and resistances were measured at rest using a duplex echo-pulsed Doppler. In order to evaluate inflight and postflight deconditioning, we used LBNP test pre, in, and postflight. The LBNP consists of two steps (-25 mm Hg and -45 mm Hg of 10 min each). During LBNP, the cerebral and femoral flow volume and resistance changes were monitored using a Doppler skin sensor, as during the HDT LBNP test. The cerebral/femoral flow ratio was also measured.
Preflight sessions occurred on days -60 and -30; inflight on days +5, +9,+12 (14-d flight), or on days +6, +12, +17 (21-d flight); and postflight at day +1, +3, +7.
28-d HDT With and Without LBNP (CNES 1987-1988)(Fig. 2)
At rest, stroke volume and cardiac output were always higher in the countermeasure group than in the control group.
Carotid flow in the control group was decreased by -5% to -10% from week 2 to the end of the HDT. Femoral flow was increased by 15-20% throughout the HDT. Carotid flow in the countermeasure group was maintained until the end of the 2nd week, then it decreased by 10% and remained stable at this level during the last 2 wk. Femoral flow was increased by 20-25% throughout the HDT.
Peripheral vascular resistance at rest in the different vascular areas investigated (brain, kidney, lower limb) was higher in the countermeasure group than in the control group. This difference, at rest, was more significant at the lower limb level than at the cerebral level. The lower limb vascular resistance decrease was progressive and of higher amplitude (-20% to-30%) in the control group; however, this decrease was limited to -15% in the countermeasure group.
25-d Spaceflight Without Countermeasures (Aragatz 1988)(Fig. 3)
The stroke volume was significantly decreased inflight (-15% to -20%); however, the cardiac output increased due to heart rate increase. The total vascular resistance decreased (-18%). The local vascular resistance decreased significantly in several areas such as the brain (-8% to -12%, day 15 and day 18); the kidneys (-10% to -18%, day 15 and day 20); and the lower limbs (-8% to -20%, day 18 and day 24). The carotid flow was maintained, whereas the cerebral flow was slightly increased. The femoral flow was slightly but not significantly increased.
30-d HDT with LBNP + Exercise Countermeasures (CNES 1990-1991)(Fig. 4)
Orthostatic tolerance evaluation. During the post-HDT tilt table test (30 min at +70°), all six control subjects had a drop in blood pressure of either 20 mm Hg (four subjects) or 10 mm Hg (two subjects), with the onset of presyncopal symptoms, and for three of them, a syncope. The HDT countermeasure subjects did not present any clinical signs of orthostatic intolerance, nor any blood pressure drop. In the countermeasure group, the heart rate increase was less marked than in the control group(5,22).
Cerebral vascular response to LBNP (Fig. 4, a and b) . When subjects did not faint the middle cerebral artery blood flow velocities showed no significant changes during the three tests pre-, in-, and post-HDT. When the subjects fainted, systolic, and especially diastolic, velocities greatly decreased (22). Countermeasures had no significant effect on velocities nor on the resistance index. Only a lesser cerebral resistance index decrease was noted in the countermeasure group during the LBNP at HDT day 15, because two subjects presented presyncopal symptoms.
Femoral vascular response to LBNP (Fig. 4, c and d) . In all 12 subjects, we observed the same kind of response during each LBNP test (pre-, in- (+15 d), and post-HDT). The systolic femoral blood flow decreased progressively during the test, the maximal decrease ranging between -30% and -60% of the basal value (5) (Fig. 4b).
Flow volume variations were not significantly different between the two groups during the pre-, in- (+15 d), and post-HDT LBNP tests. On HDT day +15, we observed a vascular resistance response of lower amplitude in both populations (at -40 and at -50 mm Hg) when compared with the response obtained during the pre-HDT LBNP test. On the other hand, in the countermeasure group, the amplitude of the vascular resistance response on the post-HDT LBNP test was significantly higher than during the 15-d HDT LBNP test and was comparable with the pre-HDT LBNP test response (Fig. 4c). The amplitude of the femoral vascular resistance increase remained insufficient in the control group post-HDT tests and similar to the response at HDT day 15.
Peripheral flow redistribution during LBNP (Fig. 4, e and f) . During LBNP, the cerebral-to-femoral flow ratio (flow redistribution index) was significantly less increased on HDT day 15 in both groups, and post-HDT in the control group only. On the contrary, this ratio increased normally during the post-HDT LBNP as with the pre-HDT in the countermeasure group. The effect of the countermeasure was clearly detected on both the femoral resistance and the flow redistribution ratio.
Antares 14-d and Altair 21-d MIR Spaceflights (1992-1993)
Adaptation at rest (Fig. 5) . Cosmonaut with cuffs: At the beginning of the flight, cerebral flow(Fm) was not significantly changed, although the cerebral resistances were slightly increased (ns). Femoral flow (Qf) was reduced (-10%), and lower limb vascular resistances (Rf) increased (+12%). Renal resistances (Rr) were slightly increased (+10%). Mesenteric (Rm) and splanchnic resistances (Rct: in the area supplied by the celiac trunk) were not different from preflight. When the cuffs were removed, cerebral flow decreased (-10% to 20%), although cerebral resistances increased until the end of the flight (+10% to +15%). Femoral flow (Qf) remained lower than preflight (-15%) at day 10 and then increased (-5%, ns). The lower limb resistances (Rf) decreased (-10% to -20%) and were unstable during this part of the flight (large fluctuations). Renal resistances decreased (from +10% to baseline). Splanchnic vascular resistances(Rct) tended to decrease throughout the rest of the flight (-10% to -15%), mesenteric resistance (Rm) did not change.
Cosmonaut without cuffs: Cerebral flow remained slightly higher than preflight (<10%; ns) whereas cerebral resistances did not increase. Femoral flow was higher than preflight (+10%), and femoral resistance significantly decreased (-10% to -20%). Renal resistance remained lower than preflight (-5% to -10%). The mesenteric and splanchnic resistances were decreased throughout the flight (-10% to -15%).
Orthostatic tolerance test inflight (Fig. 6) . Lower limb vascular response: The astronaut showed the same kind of response as the HDT control subjects did. During the preflight LBNP tests, heart rate increased progressively from the first depressurization level (-25 mm Hg) until the end of the test (-45 mm Hg). The maximal variation ranged from 20% to 30%. At the same time, the systolic femoral blood flow also decreased progressively during the test, the maximal decrease ranging from -30% to -60%. The vascular resistance increased gradually and reached a maximum of about +30% to +40% of the basal value. The femoral flow response to the progressive LBNP pressure decrease was in the same range for all the preflight tests (heart rate, blood flow, vascular resistance). In flight (day 11 Antares, 6-19 Altair) the lower limb vascular resistance increase was significantly reduced (max: +15%) at -45 mm Hg when compared with the response obtained in preflight tests. Postflight the lower limb vascular resistance response to the LBNP test remained lower than on preflight LBNP test (as in flight), but normalized on the 7th postflight day(increased resistances by 40%).
Cerebral hemodynamics: The cerebral flow response to the progressive decrease of the LBNP pressure consisted of a moderate (ns) decrease in the middle cerebral artery flow volume (less than 20%), together with the resistances (less than 10%). The amplitudes of the cerebral flow responses did not differ significantly among the LBNP tests performed pre, in, and postflight.
The cerebral-to-femoral flow ratio (flow redistribution index) increased significantly less during inflight and postflight LBNP than preflight.
Several similar changes were noticed in the peripheral circulation in both the astronauts and the HDT subjects. When no countermeasures were used, the cerebral flow was maintained despite the reduction in blood circulation volume because of a decrease in cerebral vascular resistance. This confirms the efficiency of the cerebral flow regulation as already observed during other long-term HDT or long-term flights. The renal vascular resistance was decreased in parallel with the hypovolemia. In the lower limbs, we noticed a decrease of the vascular resistance during the HDT and inflight in control subjects and a loss of the vasomotor control after the HDT and postflight during orthostatic tests. As a consequence, the redistribution ratio did not increase.
Conversely, in the HDT subjects with LBNP countermeasures, the cerebral and the renal vascular resistances stayed elevated and the femoral resistance decreased less than in the HDT subjects without countermeasures. Moreover, the lower limb's resistance and the flow redistribution ratio increased adequately during post-HDT LBNP and no hemodynamic signs of orthostatic intolerance(increased heart rate, drop in the blood flow) was observed in this group. This confirms that the vasomotor tone at rest and the vascular reactivity had recovered after repeated LBNP maneuvers. In the absence of countermeasures, the decreased femoral reactivity to the LBNP test on HDT day +15 with reduction of the cerebral-to-femoral flow ratio was associated with clear signs of orthostatic intolerance, and in all cases a drop in blood pressure during the post-HDT tilt table test. In addition, the abnormal femoral response was present without reaching the stage of clinical orthostatic intolerance. Therefore, the femoral resistance and flow redistribution ratio appear to be early predictors of orthostatic intolerance. These data were consistent with the results published by Convertino et al.(13) and Eckberg et al. (15) that showed that bed rest significantly reduces the responsiveness of the carotid baroreflex response.
Finally, our HDT studies confirm the efficiency of LBNP countermeasures and muscular exercise in preserving the vasomotor reflex in the lower limbs. The LBNP inflight and postflight showed a similar pattern to that observed in the control group. This confirms that the lower limb parameter and flow redistribution are also affected inflight.
The use of bracelets maintains stroke volume, cardiac output, blood pressure, and central venous pressure. Moreover, total peripheral resistances did not change significantly during the flight with cuffs, whereas they stayed significantly decreased during the flight without cuffs. The cerebral flow was stable with the cuffs but decreased when the cuffs were removed. The lower limb vascular resistances decreased after removing the cuffs and throughout the flight without cuffs. The vascular resistances in abdominal territories(mesenteric and the splanchnic) were slightly decreased after the cuffs were removed and throughout the flight without cuffs. These observations confirm that cuffs can temporarily prevent the decrease in vascular tone in various areas. If it is shown that the cuffs tend to prevent the expected decrease in vascular tone and significantly improve the comfort of the cosmonaut, it is not clear that this countermeasure may have an incidence on the development of cardiovascular deconditioning.
The ultrasound methods have already demonstrated their ability to detect significant changes of ventricle volume and cardiac output with a precision of about 10%. More recently, echo-Doppler methods have been successfully used for the evaluation of the peripheral blood flow with the same precision. The present studies show that Doppler is well-adapted to the assessment of the peripheral vascular resistance and to the monitoring of the peripheral flow and resistance changes during orthostatic tests.
In conclusion, these studies confirm that long-term HDT is a suitable model for simulating the cardiovascular disturbances induced by zero gravity and for evaluating the response of the subject when submitted, or not, to cardiovascular countermeasures. Transcranial Doppler allows us to continuously monitor cerebral blood flow velocities and to confirm the fact that cerebral hemodynamic regulation is quite stable when compared with other vascular areas. Moreover, the monitoring of the peripheral hemodynamics by Doppler during LBNP has been demonstrated as operational in flight. Monitoring of lower limb arterial hemodynamics could be helpful in detecting vascular deconditioning inflight and interesting for the management of the countermeasure program during spaceflights. The use of thigh cuffs prevents the loss of vascular tone at rest in deep and peripheral areas. It seems possible that this soft countermeasure may contribute to the reduction of vascular deconditioning when used throughout the flight, but this question has to be investigated in more detail.
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