Changes in lower limb volume in humans during parabolic flight

¹ Services des Explorations Fonctionnelles et d'Anesthésie-Réanimation, Hôpital Lariboisière, 75010 Paris; ² Laboratoire de Physiologie, Centre Chirurgical Marie Lannelongue, 92350 Le Plessis-Robinson, Université Paris 11 and Unité Propre de Recherche de l'Enseignement Supérieur: Equipe Associée 2397; ³ Laboratoire de Physiologie, Médecine Aérospatiale, Université Bordeaux 2, F 33076 Bordeaux Cedex; and ⁴ Laboratoire des Adaptations de l'Organisme à l'Exercice Musculaire, Unité de Formation et de Recherche Médecine Toulouse-Purpan, F 31073 Toulouse Cedex, France

	ABSTRACT

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Variations in gravity [head-to-foot acceleration (G_z)] induce hemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs to blood pooling or shifting during the different gravity phases of a parabolic flight, we measured instantaneous thigh and calf girths by using strain-gauge plethysmography in five healthy volunteers. From these circumferential measurements, segmental leg volumes were calculated at 1, 1.7, and 0 G_z. During hypergravity, leg segment volumes increased by 0.9% for the thigh (P < 0.001) and 0.5% for the calf (P < 0.001) relative to 1-G_z conditions. After sudden exposure to microgravity following hypergravity, leg segment volumes were reduced by 3.5% for the thigh (P < 0.001) and 2.5% for the calf (P < 0.001) relative to 1.7-G_z conditions. Changes were more pronounced at the upper part of the leg. Extrapolation to the whole lower limb yielded an estimated 60-ml increase in leg volume at the end of the hypergravity phase and a subsequent 225-ml decrease during microgravity. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during hypergravity and weightlessness.

gravitational physiology; weightlessness; mild hypergravity; venous return; plethysmography

	INTRODUCTION

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ACUTE VARIATIONS IN GRAVITY [head-to-foot acceleration (G_z)] induce dramatic fluid shifts in pilots and astronauts as a consequence of changes in hydrostatic pressure gradients. The resulting hemodynamic alterations are responsible for many of the consequences associated with acute gravity changes (hyper- or microgravity) (5, 30). For example, combat-aircraft pilots experience reduction in their cerebral blood flow resulting from acute acceleration and have to use anti-G devices or maneuvers to prevent loss of consciousness (22). During microgravity, venous blood shifts from the legs toward the central compartment (14, 27), resulting in a variety of hemodynamic changes, including increased pulmonary capillary blood volume (23, 29) and stroke volume (10, 15, 19). The role of the venous system as a blood reservoir is crucial for these rapid cardiovascular adaptations (4, 7, 8, 20). However, the exact contribution of the leg venous compartment to volume redistribution has never been quantified directly.

To evaluate venous volume shifts associated with acute changes in gravity, we measured leg volume changes occurring during the succession of micro- and hypergravity phases generated by parabolic flight profiles (29). The leg volume measurements were performed by using strain-gauge plethysmography in healthy, standing volunteers (2, 17, 31).

	MATERIALS AND METHODS

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Subjects. Five healthy volunteers, free of venous pathology, were enrolled in this study. Individual anthropometric data are presented in Table 1. All subjects underwent special flight physical examination and gave written, informed consent to participate in this study. Subjects were not taking any medication before and during flights. This study was approved from an ethical point of view by the French Space Agency [Centre National d'Etudes Spatiales (CNES)].

View this table: [in this window] [in a new window]   Table 1.   Individual anthropometric data at 1 Gz

Equipment and protocol. A total of six parabolic flight sessions were organized by CNES, the National Aeronautics and Space Administration (NASA), and NOVESPACE (trade society of CNES, France) at the Société Girondine d'Equipements, de Réparation, et de Maintenance Aéronautique center in Bordeaux, France, during two separate campaigns, in November 1995 and November 1996. A NASA-Johnson Space Center KC-135A aircraft was used to perform the parabolic flight profiles. Flights were managed on three consecutive days. Each flight session lasted 2.5-3 h and incorporated 30 parabolas.

Instantaneous gravity was measured continuously by using the aircraft's accelerometer. Gravity variations during a parabolic flight profile include four consecutive phases (Fig. 1): normogravity (1 G_z) before the parabola began; mild hypergravity (1.6-1.7 G_z) during the ascending phase of the parabola (20-25 s); microgravity (0 G_z), lasting for 20 s and corresponding to the top of the parabola; and a second period of mild hypergravity (1.6-1.8 G_z) during the descending phase of the parabola (20-25 s), followed by a new steady state at 1 G_z.

View larger version (17K): [in this window] [in a new window]   Fig. 1.   Schematic depicting different phases of parabolic flight profile and corresponding variations in gravity [head-to-foot acceleration (Gz)]. Circled nos., phases. Phase 1: normogravity (1 Gz), duration = 2-3 min; phase 2: mild hypergravity (1.7 Gz), duration = 20-25 s; phase 3: microgravity (0 Gz), duration = 20 s; phase 4: mild hypergravity (1.8 Gz), duration = 20-25 s.

Plethysmography measurements were performed with two Perivein apparatuses (Jansen Scientific Instruments, Liège, Belgium) by using gauges made of highly elastic tubing filled with mercury. The changes in resistance of the gauges are proportional to changes in length when variations in length are <10% of the unstretched gauge (see Plethysmography calibration).

Subjects were studied in the upright position. To keep them in a near-standing position during microgravity, they were fastened to a saddle with a seat belt, and the left foot was secured in a foot strap. The right leg hung freely, and subjects, wearing tennis shoes, were asked to avoid muscular contraction using this limb during the entire parabola. Four strain gauges were placed around the right leg at precise locations that were marked by using a dermographic pencil. Two gauges were placed on the thigh: one at the junction between the upper third and the lower two-thirds of the thigh and the other one at the minimum circumference above the knee. On the calf, the two gauges were placed at the maximum calf girth and 5 cm above the lateral malleolus, respectively. Each girth, as well as the distance between gauges, was measured with a ribbon meter (Fig. 2). Gauge sizes were selected according to thigh and calf girth, as recommended by the manufacturer's specifications. When thigh girth was >40 cm, we used an adapter (flexible and unexpandable) for correct fitting of the gauge.

View larger version (15K): [in this window] [in a new window]   Fig. 2.   Schematic depicting gauge positioning on right leg. Two gauges were placed around the thigh (gauges 1 and 2) and 2 around the calf (gauges 3 and 4). h1 and h2: Distance separating gauges on thigh and calf segment, respectively.

Plethysmography calibration. The linearity of gauge response to length changes was tested on a bench before the experiment, and the regression line for each gauge was determined. Static stretching at three different lengths (<10% total length) was imposed at each gauge for 20 s and was found to yield linear changes in resistance. Reproducibility was assessed by repeating stretching five times for each length tested. No drift in resistance was noted after prolonged stretch (>100 s), and a return to baseline resistance was verified. Resistance increased linearly when the stretching was <10% of the unstretched length. Gauge responses with or without adapter were effectively linear.

To ensure that changes in gravity had no significant effect on strain-gauge plethysmography, we placed four gauges on a dummy limb (plastic model) during a parabolic flight and recorded data during 30 parabolas. No noticeable change in gauge length (<0.001 cm) was recorded during the parabolas.

Data acquisition. Data were digitized by using an analog-to-digital board (Daqbook 100 Iotech, Cleveland, OH) and stored on the hard disk of an AST (Ascentia 900N) 486 microcomputer for off-line signal processing. On-line display allowed immediate control of the signal quality. Each gauge was connected to a separate channel, and the four plethysmographic signals were acquired simultaneously along with instantaneous acceleration. Data were sampled at 2.5 Hz for 100 s with a precision of 12 bits. Data acquisition was initiated 20 s before each parabola on NASA crew member's warning. Each channel of the plethysmographic apparatus was reset to 0 V before data acquisition began.

Data analysis. Parabolas were considered suitable for analysis when all phases of the parabolic flight profile were clearly distinguishable and no obvious artifactual variations in length (i.e., muscular contraction) were noted.

Only the first three phases of the parabolic flight profile were analyzed in the present study. Baseline (normogravity) limb segment girths were taken as the values measured with the ribbon meter before takeoff. Mild hypergravity and microgravity data were averaged from plethysmographic recordings obtained during the last 4 s (corresponding to the plateau) of hyper- and microgravity phases, respectively, by using all available parabolas. The fourth phase was not analyzed quantitatively because the lengthening in leg girths did not reach a clear plateau before the return to horizontal flight and normogravity (Fig. 3). The absence of significant change in limb segment girth profile related to repetition of parabolas was ensured by appropriate statistical testing (see Statistical procedures).

View larger version (19K): [in this window] [in a new window]   Fig. 3.   Representative example of instantaneous gravity and plethysmographic variations recorded simultaneously during whole sequence of parabola. Note that changes in girth are almost negligible at lower calf.

Segmental leg volumes of the thigh and calf segments between two gauges were subsequently calculated from circumferential measurements as (13) where V is volume (ml), h is the distance between gauges, C₁ is the upper girth (gauge 1 or 3), and C₂ is the lower girth (gauge 2 or 4) (see Fig. 2). This computation was repeated for each phase of the parabolic flight by using the corresponding girths.

To estimate the volume of the entire lower limb at 1 G_z, we calculated whole thigh and whole calf volumes according to the above equation from girths measured at the root and base of the thigh and calf. Lower limb volume at 1 G_z was the sum of whole calf and whole thigh volumes. Variations in lower limb volume relative to 1-G_z conditions during hyper- and microgravity were extrapolated by applying the percent variation of each segment to the whole thigh and the whole calf, respectively.

Statistical procedures. A two-way ANOVA was used to assess the absence of variability among different parabolas in each subject. To compare the values obtained during the different phases of parabolic flight, a Friedman repeated-measures ANOVA on ranks was used because assumptions of normal distribution and equal variance were not fulfilled. A P < 0.05 was considered significant.

	RESULTS

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One hundred and fifty parabolas were acquired with study subjects, but only fifty fulfilled the above-mentioned criteria for analysis. Accordingly, 8-12 parabolas were available for each subject. In addition, 30 parabolas were performed with the dummy limb. The variability of G_z values among parabolas is presented in Table 2.

View this table: [in this window] [in a new window]   Table 2.   Variability of Gz values at different phases of parabolic flight

A representative example of simultaneous changes in gravity and gauge responses during the entire sequence of a parabola is presented in Fig. 3. In the absence of muscular contraction, the girth signal always returned to baseline. Limb segment volume variations during hyper- and microgravity were not altered by repetition of parabolas (P > 0.50).

Individual values for limb segment circumferences according to different gravity phases were found to be very reproducible with repetition of parabolas (within-subject SDs: 0.3 mm during hypergravity and 0.6 mm during microgravity). Mean ± SD and median leg segment girths (cm) are presented in Table 3. We observed significant increases and decreases in leg segment volumes secondary to mild acceleration (hypergravity) and microgravity, respectively. Mean ± SD and median values for thigh and calf segment volumes during normo-, hyper-, and microgravity are presented in Table 4. Individual percent changes in calf and thigh segment volume, relative to 1-G_z conditions, are presented in Fig. 4.

View this table: [in this window] [in a new window]   Table 3.   Mean ± SD and median leg segment girths at different phases of parabolic flight

View this table: [in this window] [in a new window]   Table 4.   Thigh and calf segment volumes at different phases of parabolic flight

View larger version (11K): [in this window] [in a new window]   Fig. 4.   Individual fractional change in calf (A) and thigh (B) leg segment volume at end of mild hypergravity (1.7 Gz) and microgravity (0 Gz), with respect to normogravity (1 Gz). Symbols and lines of 2 subjects overlap in A and B.

The estimated increase in leg volume during mild hypergravity with respect to normogravity was 0.9% for the thigh and 0.5% for the calf (whole leg volume variation was +60 ml on average). The mean volume reduction secondary to microgravity after mild hypergravity was 3.5% for the thigh and 2.5% for the calf (whole leg volume variation was 225 ml on average).

	DISCUSSION

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For a better understanding of the hemodynamic alterations observed during parabolic flights, we quantified the volume changes in lower limbs resulting from the variations in gravity by using strain-gauge plethysmography in healthy, standing volunteers. We found an average 0.8% increase in whole leg volume after a 16-s exposure to mild hypergravity (1.7 G_z) relative to 1-G_z conditions. Sudden exposure to microgravity (0 G_z) after mild hypergravity induced a mean reduction of 3.1% in whole leg volume relative to 1.7-G_z conditions. These volume changes probably correspond to blood pooling in the leg venous system during hypergravity and subsequent shifting toward the central venous compartment as a consequence of microgravity (5, 27, 30).

Methodological considerations. Parabolic flight is the most convenient method of studying physiological changes related to sudden exposure to microgravity and mild hypergravity in humans. Subjects were studied in the standing position to maximize the vertical hydrostatic pressure gradient. The sequence of gravity variations generated during the parabolas presented in this study was similar to that described previously (29). Some variability existed among parabolas regarding the absolute value of G_z obtained at the different phases studied. Mean values ± SD for G_z at the different phases studied are presented in Table 2. Additionally, for technical reasons, the parabolic flight profile was not exactly symmetrical; i.e., the transition between 1.7 and 0 G_z was shorter than that between 0 and 1.7 G_z (3.5 ± 1.0 vs. 5.2 ± 1.4 s, respectively, P < 0.001).

In this study, we used strain-gauge plethysmography to quantify volume changes in limb segments during parabolic flight. Other investigators have used the same technique to explore the venous system under various conditions (2, 6, 17). To our knowledge, there has been no previous attempt to assess the effects of acute changes in gravity on limb volumes with this technique. The volume of the limb segment was calculated by assuming that it has the shape of a truncated cone. This assumption has been validated (13) and is widely accepted (6, 12, 18, 26). However, because the actual geometry of limb segments is more complex than a simple, truncated cone, these volume values should be interpreted with caution. The foot and the knee were not taken into account in computing changes in whole leg volume. Indeed, the knee is a bony structure with little vascular capacitance (28). The foot was in a tennis shoe, and its volume variations have been neglected. The volumes calculated in the present study for whole thigh and whole calf at 1 G_z were similar to those reported by Katch and Weltman (13) for subjects of the same gender (thigh: 5.5 ± 3.1 vs. 6.3 ± 1.2 liters; calf: 1.8 ± 0.5 vs. 1.8 ± 0.2 liters; present study vs. Katch and Weltman, respectively).

Present findings. The changes in girth lengths measured in this study were due to changes in leg volumes because no lengthening was observed on the dummy limb during parabolic flights. These changes were probably related to changes in venous blood volume because the venous compartment is the most compliant of all limb compartments (i.e., arterial, venous, bone, and muscle). Interstitial fluid cannot be involved during the 20-s periods of the different gravity phases because of the time required for such shifts (9).

The coefficient of variation of girth lengthening among the different parabolas was 10% and may be related, in part, to the relative dispersion (variability) in G_z (Table 2). Girth changes were more pronounced at the upper thigh and almost negligible at the lower calf. This finding is not surprising because the relative volume of the venous compartment is greater in the upper part of the leg and decreases toward its lower extremity (12). All girth lengths increased progressively during mild hypergravity and reached a plateau before the end of this phase (Fig. 3). The calculated mean increase in leg volume at the end of mild hypergravity relative to 1-G_z conditions was 60 ml, corresponding to 0.8% of total leg volume (0.9% for the thigh and 0.5% for the calf). To the best of our knowledge, there are no other data quantifying leg volume increases during mild hypergravity (1.7 G_z) in the standing position. The venous blood pooling in the lower limbs is secondary to the increase in hydrostatic pressure resulting from increased G_z (5, 22). The superficial venous system is probably predominantly involved in blood pooling because tissue pressures are greater in deep muscular than in superficial subcutaneous tissues (1), and therefore the transmural pressure increase is greater in the superficial than in the deep veins.

Sudden exposure to microgravity induced a shortening in girth length corresponding to a 225-ml leg volume reduction, representing 3.1% of the total leg volume relative to 1.7-G_z conditions (3.5% for the thigh and 2.5% for the calf). Venous blood emptying was mainly due to the reduction in transmural pressure, allowing for recoil of the previously distended veins. Nevertheless, in upright subjects, an increase in central venous pressure as been noted by Norsk et al. (21) during parabolic flight. Therefore, this increase in central venous pressure would tend to counteract leg venous blood emptying. However, this effect would be small in view of the large probable reduction in leg venous pressures. Again, volume changes were more pronounced in the upper part of the limb, in agreement with the findings of Thornton et al. (27) during prolonged spaceflight. This emphasizes the poor relevance of ground-based models (head-down tilt position or water immersion) to simulate microgravity, because these maneuvers generate an opposite pattern of segmental limb volume variations, i.e., more pronounced changes in the calf than in the thigh (26). This discrepancy may be due to the different alterations in both transmural and hydrostatic pressures resulting from true changes in gravity as opposed to body positioning and/or immersion.

The fourth phase of parabolic flight corresponds to a gravity increase from 0 G_z back to 1.7 G_z. This phase was not analyzed quantitatively because the lengthening in leg girths did not reach a clear plateau before the return to horizontal flight and normogravity (Fig. 3). Although the fourth phase was longer in duration than the second phase because of the asymmetry in parabolic flight profile (see Methodological considerations), the girth lengths did not return to preemptying values. Because lower limb veins have valves to prevent venous backflow, blood volume increase in the leg can only result from arterial filling. To refill the leg with 225 ml within 25 s, femoral arterial flow should be 540 ml/min, whereas resting supine arterial flow values are usually 120 ml/min (25). Because the femoral arterial bed is vasoconstricted (3) and cardiac output is reduced (10) during mild hypergravity, the refill of the leg takes longer than does the emptying. However, after 2 min of horizontal flight at 1 G_z, all girth lengths had returned to baseline.

The volume changes measured during acute variations in gravity (parabolic flight) are somewhat different from the chronic alterations measured during long-term exposure to microgravity. Moore and Thornton (18) calculated an 8.4% decrease in whole leg volume after 10 h of spaceflight in the space shuttle, and Thornton et al. (27) reported as much as a 12.5% decrease after 48 h in Skylab. These larger volume reductions after longer exposure to microgravity may result from a reduction in total plasma volume (4 to 13%) observed in astronauts (11) and from slow interstitial fluid shifts (9).

Our results concerning the volume variation in lower limbs are different from other studies, which report "a blood or other fluid shift of 1 to 1.5 liters from the legs to the upper body when subjects experienced zero-gravity" (16, 24). However, these changes were observed under conditions of long-term exposure to microgravity. In addition, in these previous studies the authors used impedance tomography, which monitors whole fluid changes in the chest, not only the fluid shift from the lower limbs. The contribution of the abdomen to central blood volume changes may partly explain this difference (9).

Conclusions. Acute variations in gravity generated by parabolic flight profiles result in significant variations in leg volume, most probably corresponding to venous blood shifts. These variations are predominant at the root of the limb, unlike those observed in ground-based models of microgravity relying on immersion or positioning. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during mild hypergravity and weightlessness.

	ACKNOWLEDGEMENTS

We appreciate the dedicated collaboration of the NASA crew of the KC-135 aircraft. We thank P. Winterton for critically reviewing the English version of the manuscript.

	FOOTNOTES

P. Vaïda was the recipient of grants from the Centre National d'Etudes Spatiales (95/CNES/324) and the Conseil Régional d' Aquitaine (94 0302002).

Address for reprint requests: P. Vaïda, Laboratoire de Physiologie, Médecine Aérospatiale, Université Bordeaux 2, F-33076 Bordeaux Cedex, France (E-mail: Pierre.Vaida{at}u-bordeaux2.fr).

Received 27 October 1997; accepted in final form 31 July 1998.

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