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Eur J Appl Physiol (2003) 90: 283–291 DOI 10.1007/s00421-003-0884-5

R EV IE W A RT I C L E

G. Antonutto Æ P. E. di Prampero

Cardiovascular deconditioning in microgravity: some possible countermeasures

Accepted: 7 May 2003 / Published online: 8 July 2003  Springer-Verlag 2003

Abstract Microgravity is an extreme environment inducing relevant adaptive changes in the human body, especially after prolonged periods of exposure. Since the early sixties, numerous studies on the effects of microgravity, during manned Space flights, have produced an increasing amount of information concerning its physiological effects, globally defined ‘‘deconditioning’’. Microgravity deconditioning of the cardiovascular system (CVD) is briefly reviewed. It consists of: (1) a decrease of circulating blood and interstitial fluid volumes, (2) a decrease of arterial blood diastolic pressure, (3) a decrease of ventricular stroke volume, (4) a decrease of the estimated left ventricular mass and (5) resetting of the carotid baroreceptors. The negative effects of microgravity deconditioning manifest themselves mostly upon the reentry to Earth. They consist mainly of: (1) dizziness, (2) increased heart rate and heart palpitations, (3) an inability to assume the standing position (orthostatic intolerance), (4) pre-syncopal feelings due to postural stress and (5) reduced exercise capacity. To avoid these drawbacks several countermeasures have been proposed; they will be briefly mentioned with emphasis on the ‘‘Twin Bikes System’’ (TBS). This consists of two coupled bicycles operated by astronauts and counterrotating along the inner wall of a cylindrical Space module, thus generating a centrifugal force vector, mimicking gravity. Keywords Bed rest Æ Cardiovascular deconditioning Æ Countermeasures Æ Microgravity Æ Parabolic flight

G. Antonutto (&) Æ P. E. di Prampero Dipartimento di Scienze e Tecnologie Biomediche and M.A.T.I. Centre of Excellence, P. le M. Kolbe 4, 33100 Udine, Italy E-mail: [email protected] Tel.: +39-432-494334 Fax: +39-432-494301

Introduction From birth onwards, gravity acts on the human body pulling it towards the centre of the Earth with a force equal to body weight, i.e. to the product of body mass times the acceleration of gravity (g=9.81 mÆs)2 at 45 of latitude). On Earth, weightlessness can be reproduced, even if for very short periods of time (20–30 s), on board aircrafts performing parabolic manoeuvres. In this case the aircraft, and its content, moves under the action of gravity, free-falling during part of its parabolic trajectory. However, since the aircraft moves into the terrestrial atmosphere, the aerial friction against the external walls of the aircraft, during the weightlessness phase, must be balanced by the thrust of the engine, a fact which makes it difficult to attain a perfect ‘‘zero-g’’ condition. This environmental situation is therefore defined ‘‘microgravity’’, the residual g intensity amounting to 10)2–10)4 g. In addition, since the trajectory described by the aircraft before and after the weightlessness period of the parabola is curved upwards, a complete parabolic manoeuvre also includes two phases during which the aircraft and its content are pulled toward the ground by the vectorial sum of gravity and the centrifugal force amounting to about 1.8 g. For of these reasons, parabolic flights are limited to the study of those systems which adapt very rapidly to weightlessness and which are not greatly affected by the hyper-g phases preceding and following the parabola. Weightlessness is a more stable condition when orbiting around the Earth. In the case of Space vehicles at an altitude of 350 km, gravity pulls them towards the centre of Earth with an intensity of 90% of its value at sea-level. The vehicle and the astronauts within it fall continuously toward the Earth, but because of their high tangential velocity (about 29,000 km/h) they continuously ‘‘overshoot and miss the Earth entirely’’ (Hall 1994). Therefore, the contents of Space stations, objects or humans, freely float into the internal atmosphere if

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not retained to the internal walls of the vehicles. Also the environmental conditions of Space vehicles orbiting around the Earth can be described as ‘‘microgravity’’, because of the inevitable residual vibrations. When Space vehicles move away from Earth, the effects of g decrease with increasing distance. This was the case of the Apollo missions to the Moon. For the first time in history, in July 1969 three astronauts (E. Aldrin, N. Armstrong and M. Collins) onboard Apollo 11 left the terrestrial gravitational field to be captured by the gravitational field of the Moon at about 48,000 km from its surface, where, because of the smaller mass of the Moon as compared to the Earth, the acceleration of gravity is 1/6 g=1.623 mÆs)2. In conclusion, the exposure to microgravity can be of very short duration, as observed during parabolic flights, or prolonged for days or months during Space flights. The longest continuous exposure to microgravity observed as of today is that of the Cosmonaut V. Poliakov, who stayed 438 days on board the Space Station MIR orbiting around the Earth.

Effects of terrestrial gravity on the human cardiovascular system The evolution of Man took place in the constant gravitational environment of Earth; as a consequence, some systems of the human body function ‘‘because of’’ gravity, whereas some others function ‘‘in spite of’’ gravity. The cardiovascular system fulfills the latter description, delivering blood in just the right amounts and at appropriate pressures, despite gravity (Churchill and Bungo 1997). Humans usually maintain the upright position, and therefore 70% of the blood contained in the human body is located below the heart level. In contrast, in quadrupeds 70% of the blood is located at or above the heart level, along the nearly horizontal axis of the aorta. The term ‘‘pooling’’ is utilized in humans to describe the displacement of blood away from the thorax to peripheral veins. The ‘‘pooled’’ blood is not stationary, but its mean transit time through the dependent region is increased because of the increased volume (Rowell 1986). This is expressed formally by the large time constant of the venous system: s=RvÆCv, where Rv represents the small, but important, circulatory resistance of the venous system, whereas Cv represents the large venous compliance (Rowell 1986). When a person is standing in the upright position the mechanical action of the heart generates a dynamic pressure which is equal to the cardiac output (CO, lÆmin)1) times the total peripheral resistance (TPR, mmHgÆl–1Æmin, where 1 mmHg equals 133.322 Pa) of the circulatory system. Normally, the mean pressure generated by the heart is equal to 100 mmHg at the aortic bulb level. However, two other components contribute to the overall blood pressure: (1) a static pressure (7 mmHg), due to the elastic characteristics of the vascular system,

independently of the flow of blood, and (2) a hydrostatic component, due to the force of gravity, equal to qÆgÆh, where q is the blood density, g the acceleration of gravity and h the height of the vertical column of blood above (negative: )qÆgÆh) or below (positive: +qÆgÆh) the heart level. This means that the heart works ‘‘in spite’’ of gravity when it pumps blood to the head. On the other hand, blood pools to the feet ‘‘because of’’ gravity, but it must be recovered ‘‘in spite’’ of gravity to return from the feet to the heart. In the supine position, head, heart and feet are at the same level and the mean pressure is almost the same throughout the arterial system, since the term ‘‘qÆgÆh’’ is negligible. This is what normally happens when we lie in bed, in which condition most of our blood volume is stored in the large and highly compliant veins of the chest and abdomen. When we rise, the circulatory system is suddenly exposed to the gravitational stress, leading to the immediate appearance of a significant hydrostatic component of blood pressure. In healthy individuals, the immediate pooling of blood in the lower limbs and the difficulty of perfusing the brain, due to the hydrostatic column located between the heart and head, is compensated for by a beat-to-beat mechanism, ruled by the sympathetic nervous system. This assures a satisfactory venous return from the lower part of the body to the right atrium, and an effective pumping action of the heart, pushing the blood to the brain, against gravity.

Effects of microgravity on the human cardiovascular system The rapid transitions from the upright to the supine position, made possible by a tilting table, simulate the sudden exposure to microgravity occurring during parabolic manoeuvres. Therefore, the acute circulatory compensatory mechanisms, at the rapid onset of simulated microgravity, can be studied utilizing a tilting table. Moreover, during the up-right to horizontal tilt and vice versa, the phases of hyper-gravity (20–25 s at 1.8–2 g) that typically precede and follow the microgravity period of the parabolic manoeuvres do not occur and, therefore, do not interfere with the physiological responses taking place during the transition from eugravity to simulated microgravity. There are two main cardiocirculatory adjustments which can be observed during acute transitions from eu- (or hyper-) gravity to microgravity: (1) a dramatic decrease of the heart rate (HR, Fig. 1a) and (2) an increase of the stroke volume of the left ventricle (SV). According to Linnarsson et al. (1996) the first is due to a compensatory response, driven mainly (85%) by the carotid baroreceptors and to a minor extent (15%) by the cardiopulmonary volume receptors. The increase of SV is driven by the Frank– Starling mechanism. In fact, during the microgravity phase the venous return is increased because of the shift of blood into the thorax from the lower half of the body where it was pooled during hypergravity (in the case of

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Fig. 1 a Heart rate (right ordinate, HR, beatsÆmin)1), as a function of time, of a subject exercising on a cycloergometer at 120 W during one parabolic manoeuvre. b Stroke volume of the left ventricle (right ordinate, SV, ml) of the same subject during the same parabolic manoeuvre. In both panels, continuous lines indicate the ±Gz vector (1 Gz=9.81 mÆs)2, left ordinate) recorded by means of an accelerometer located on board the aircraft

parabolic manoeuvres) or, less dramatically, during the previous upright position of the body (in the case of tilting manoeuvres). The time course of SV during a parabolic manoeuvre shows a waveform that is opposite in phase with the time course of g (Fig. 1b). The physiological responses to acute and short (tenths of seconds) exposure to microgravity are different from those brought about by a prolonged (days or more) exposure. Since the early years of the Space era it was clear that prolonged exposure to microgravity induced a series of consequences at the cardiocirculatory level which were globally defined as ‘‘cardiocirculatory deconditioning’’ (Charles et al. 1994; Hinghofer-Szalkay 1996; Churchill and Bungo 1997). The first episode of postflight orthostatic intolerance (one of the symptoms of cardiocirculatory deconditioning) was reported in October 1962 upon reentry to Earth of the astronaut W. Schirra, after 9 h and 13 min on board the Mercury 8 spacecraft (Nicogossian et al. 1994). In these early years of the Space era however, the attention of Space physicians was focused more on neurovestibular and overheating, than on cardiocirculatory, problems. These were extensively investigated from the early seventies onward. During the flight of Apollo 15 (1971: 12 days and 7 h, 4th lunar landing) cardiac arrhythmia and extrasystoles were reported. From the first U.S. Space Station Skylab 2 (1973: 28 days, the first U.S. physician

in Space) regular and extensive biomedical monitoring of the crews were performed, and during the Skylab 4 flight (1973: 84 days) the countermeasures to prevent cardiovascular deconditioning (CVD) were increased. A cardiovascular index of deconditioning (CID= DHR)DSBP+DDBP, i.e. change in HR minus the change in systolic blood pressure plus change in diastolic blood pressure) was proposed by Charles and Lathers (1991) to evaluate the effectiveness of inflight CVD countermeasures. Unfortunately, however, the CID turned out to be the same (ranging from 30 to 35) after 10 days of Space flight in subjects who utilized countermeasures and in subjects who did not (Charles and Lathers 1991). On Earth, the effects of prolonged exposure to microgravity have been and are studied during head down tilt (HDT )6) bed rest, which simulates in a rather satisfactory manner the effects of microgravity on the cardiocirculatory and muscle functions (Fortney et al. 1996; Sundblad et al. 2000; Spaak et al., 2001). The primum movens of the physiological response to prolonged exposure to microgravity is the shift of body fluids toward the head and thorax. This cephalad fluid shift is witnessed by the in-flight photographs showing the facial puffiness of the crew members. Puffy faces, engorgement of the neck veins and decrements in calf girth (chicken legs) all appear within the first 24 h of flight and reach a steady state in 3–5 days (Hoffler et al. 1977). The fluid shift distends the central vasculature and this is ‘‘read’’ as a fluid-volume overload mainly by the so called volume sensors of the cardiovascular system located in the walls of the vena cava, of the pulmonary vasculature and of the atria. An integrated two-step cardiovascular-neuro-endocrine response follows: (1) an immediate reduction of TPR together with a slowing down of heart rate and a reduction of cardiac inotropism and (2) a reduction of the circulating volume, because of increased water excretion by the kidney. The kidney is ‘‘informed’’ about the circulatory overfilling by circulating hormones and, probably, by a decrease of sympathetic tone of its arterioles. The hormones involved in the renal response to prolonged exposure to microgravity are mainly renin-angiotensin, aldosterone and antidiuretic hormone (ADH). The functional loop increasing the renal excretion of water and electrolytes, similar to the Henry-Gauer reflex, is started by the onset of microgravity exposure which causes the central volume fluid shift. The consequent rise of the venous (low) pressure causes the increase of filling pressure of the right atrium (preload). A central reflexive inhibition of release of ADH, aldosterone and renin-angiotensin leads finally to the increased renal excretion of water and electrolytes. Renal excretion of sodium and water is synergistically regulated by atrial natriuretic peptide (ANP) as well, a hormone released by atrial cells stretched by the increased venous return. According to Russian scientists (Gazenko et al. 1985; Yegorov et al. 1988a, 1988b), the relatively rapid responses of the cardiovascular system to microgravity

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exposure are: (1) a decrease of plasma volume, (2) a decrease of circulating blood and interstitial fluid volumes, (3) a relative increase of the mass of erythrocytes and hemoglobin and (4) a decrease of arterial blood diastolic pressure. Delayed adaptive reactions include a further decrease in circulating blood volume, due to inhibited erythropoiesis, and a consequent decrease of erythrocyte mass and hemoglobin concentration (Lane et al. 1996). The blood flow to the heart reaches a new equilibrium point characterized by decreased stroke volume and diastolic blood pressure. The final effect of the above compensatory mechanisms, as the time of exposure to microgravity increases, is the establishment of a new set point of the cardiocirculatory system, different from that which is in force on Earth (Fig. 2). Fig. 2 Schematic representation of the integrated physiological effects of exposure to microgravity. Cardiovascular rapid and delayed adaptive reactions are reported. From Gazenko et al. (1985) and Yegorov et al. (1988a)

In other words, the cardiocirculatory system is now ‘‘deconditioned’’ with respect to the gravitational field, showing a decreased tolerance to gravity which becomes fully appreciable upon return to Earth. Cardiovascular deconditioning also includes carotid baroreceptor resetting. Indeed, when living in the terrestrial eugravitational environment, the prevailing blood pressure at the carotid sinus level, where arterial baroreceptors are located, is equal to the pressure at the aortic bulbus minus a quantity equal to ‘‘qÆgÆh’’, where h is the distance between the two anatomical sites. In microgravity, the hydrostatic pressure component ‘‘qÆgÆh’’ tends to zero and, therefore, the carotid baroreceptors are stimulated by a corresponding increase of carotid distending pressure (CDP) which gives rise to a carotid baroreceptor vagal-cardiac reflex whose overall, chronotropic and inotropic effects on myocardium lead to a decreased effectiveness of the cardiac pump. The sigmoid relationship between CDP and R-R intervals of

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Fig. 3 R-R interval (ms) as a function of the carotid distending pressure (mmHg), before and after (R+0) Space Shuttle flights (4–5 days). Larger symbols indicate operational points. After flight the S-shaped relationship between the two variables is displaced to a lower level, but the operational range and the slope of the linear tract are approximately the same. (Modified from Fritsch et al. 1992)

the heart beats shows a down-regulated resetting of the carotid baroreceptor’s response which becomes apparent even after short (4–5 days) exposure to microgravity (Fig. 3). The reduced R-R interval response to CDP persists up to 10 days after landing, contributing to the orthostatic hypotension (Fritsch et al. 1992). This rapid onset response of the carotid baroreceptors to the arterial (high) pressure changes is followed by stimulation of the (low) pressure baroreceptors of the central veins and of atrial stretch receptors, due to the cephalad fluid shift, which, as described above, triggers the renal excretion of water and sodium. For practical purposes the loss of water and salt can be evaluated monitoring the changes of plasma volume and total body water (TBW) (Leach Huntoon et al. 1994; Churchill and Bungo 1997). Data reported by Johnson et al. (1977) showed a stabilized 12% decline of plasma volume within hours of Space flight. Leach and Rambaut (1977) measured TBW in nine crewmembers of a Skylab mission before and after Space flight showing a 1.7% loss. Leach et al. (1991) found a 3.4% decrease of TBW after 1–3 days of a Shuttle flight. Since the pioneering study of Henry et al. (1977), echocardiography has been used to investigate the effects of microgravity on heart function before, during and after Space flights. The most relevant findings are the decreases of the stroke volume (SV, ml), of the ventricular end-diastolic volume and of the estimated left ventricular mass (Henry et al. 1977; Charles and Lathers 1991). A substantial fall of SV after Space flight in two subjects participating to the Euromir ’94 mission was also observed utilizing together CO2-rebreathing (Fahri et al. 1976) and pulse contour (Antonutto et al. 1994, 1995) methods (Antonutto et al., unpublished observation). Indeed, 2 days after reentry to Earth (R+2) from

31 days of Space flight, in one subject SV was reduced by 17%. In the second subject, who spent 171 days on board the MIR Space station, SV at rest was similar to the pre-flight value at R+3, presumably because of the use of thigh and leg cuffs, but decreased by 36% at R+8 at which time the cuffs had been removed (Antonutto et al., unpublished observation). Echocardiographical studies show that cardiac function and myocardial contractility do not deteriorate. In fact, by plotting ventricular end-diastolic volume versus SV, the curves follow a straight line despite decreased cardiac size and SV (Charles et al. 1994). It can be concluded that the apparently reduced ventricular mechanical performance is due to extrinsic causes (Frank–Starling mechanism) rather than to intrinsic ones (changes of myocardium mass and/or contractility). This opinion, however, is not shared by Sundblad et al. (2000) who observed that the cardiovascular response to exercise after 6 weeks of HDT bed rest was impaired for a long period of time (R+32), suggesting that structural cardiac changes had developed during the HDT period. Recently, Cautero et al. (2003) found a 14% average decrease of maximal O2 consumption (V_O2max) in nine subjects who participated to a 14-day HDT bed rest study. So, in this initial phase, the average rate of decrease of V_O2max was 1% per day. In the same subjects, HR at steady state turned out to be higher after HDT bed rest at the same submaximal work loads, thus indicating: (1) a smaller O2 pulse (V_O2/HR; ml O2 per beat), and (2) a remarkable decrease ()16%) of SV values after HDT bed rest, as compared to control subjects. These latter subjects were confined for the same time and in the same confined environment as the HDT subjects, but they did not perform any physical exercise and rested in bed only during the night when asleep. The above-described physiological adaptations to microgravity or, better, de-conditioning to eugravity give rise to problems upon return to Earth of Space crews. At a first glance, even laymen were able to realize from TV reports the severe physical debilitation of the cosmonauts leaving the Soyuz vehicles after long-duration Space flights. Their faces appeared sweaty and pale and they moved only with the help of other people and, to prevent them from fainting, they immediately sat down. Moreover, during the days immediately following the reentry, they wore cuffs on their thighs to prevent blood pooling. This is not the case for the crews reentering from Shuttle missions because of their shorter duration. The term ‘‘cardiovascular deconditioning’’ (Bungo and Johnson 1983; Bungo et al. 1987) summarizes the different symptoms affecting the Space crews upon reentry to Earth. They are mainly dizziness, increased heart rate and heart palpitations, an inability to assume the standing position (orthostatic intolerance), pre-syncopal feelings due to postural stress and reduced exercise capacity. Orthostatic intolerance and a pre-syncopal feeling, approaching loss of consciousness, are due to inadequate perfusion of the brain. The impairment of the overall cardiocirculatory response to gravitational

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stress is caused by the ineffective control of blood pressure due to the resetting of carotid baroreceptors and to the loss of fluid volume and to the consequent mismatching of the beat-to-beat adjustment of the cardiac output (i.e. SV) to venous return (i.e. end diastolic ventricular volume) equivalence. The decreased exercise capacity, however, is only in part attributable to the cardiocirculatory deconditioning since some is due to musculoskeletal decay, which is also an effect of microgravity exposure. Similar findings were observed from subjects who participated in prolonged periods of HDT bed rest experiments (Ferretti et al. 1998). Complete recovery of cardiovascular function is reported at about 10 days after short-term Space flights (4–10 days). However, according to Russian scientists, a period of 4 weeks is required for full recovery of cardiovascular function after long-term (8–12 months) Space flights (Churchill and Bungo 1997).

Countermeasures to cardiovascular deconditioning Since the early reports of CVD following short and prolonged Space missions, scientist have studied and tested different countermeasures to prevent both CVD and reduced exercise capacity. The prevention of orthostatic intolerance has become of crucial importance for Shuttle flights, where reentry to the terrestrial atmosphere and landing are directly piloted by crew members whose physical fitness must not be hampered by the g forces during de-orbiting and the manoeuvres related to landing. Nowadays, countermeasures include: (1) on-board physical exercise consisting of cycloergometric and/or treadmill exercises for at least 2 h per day; (2) utilization of special elasticized suits (‘‘Penguin’’ suits) providing passive stress of antigravity muscles of the legs and torso, worn by astronauts for approximately 8 h/day; (3) lower body negative pressure (LBNP) devices and (4) ingestion of water and salt tablets, up to 1 litre of saline solution, just before the beginning of Shuttle’s reentry and landing manoeuvres. Physical exercise, carried out daily according to different protocols, maintains the loss of aerobic exercise capacity within )20% of the pre-flight value of V_O2max. In contrast, in spite of these ‘‘aerobic’’ countermeasures, the explosive power of the lower limbs is much more affected by microgravity exposure: )30% of the preflight value after 1 month and )60% of the preflight value after 6 months on board the Space station MIR (Antonutto et al. 1999). It should also be pointed out that onboard the MIR station, the Astronauts did not perform any exercise specifically aimed at preventing the decay of the explosive power of the lower limbs. This decay of muscle function has been attributed mainly to a resetting of the neuromotory control system, since the decrease of the muscle mass alone (from )9% to )13%, Zange et al. 1997) did not completely justify these findings (Minetti 2002; Zamparo et al. 2002).

Data collected after HDT bed rest experimental studies without countermeasures yield similar results. Also in this case the most common findings are reduced orthostatic tolerance, reduced exercise capacity (V_O2max decrease of about 20%) and resting heart rate values greater that those recorded before bed rest (Cautero et al. 2003; Ferretti et al. 1998). The similarity between bed rest and Space flight breaks down, however, when the explosive power of the lower limbs is considered. Indeed the fall of explosive power after bed rest ()23.7% after 42 days, Ferretti et al. 2000) is substantially smaller than after Space flight, a fact which supports the view that the decay of muscle explosive power is due to a rearrangement of motor coordination brought about by microgravity. Indeed, during bed rest, the pull of gravity is not abolished; it is simply shifted by 90, as compared to the body axis. As such, gravity proprioception is maintained and the fall of explosive power is essentially equal to what could be expected on the basis of the observed fall of muscle mass (Zamparo et al. 2002). For a detailed review of the effects of microgravity on the musculoskeletal system the reader is referred to di Prampero and Narici (2003). A promising approach to prevent CVD is to re-create artificial gravity in Space (White 1965), especially during Space missions of long duration. To this end, short-radius centrifuges located on board the Space stations have been proposed by several authors (Burton 1997; Burton and Meeker 1994; Cardu`s 1994; Greenleaf et al. 1997; Hastreiter and Young 1997; Vernikos 1997; Vil-Viliams et al. 1997). In 1991, we proposed the ‘‘Twin Bikes System’’ (TBS) consisting of two coupled bicycles, ridden by two astronauts, counter-rotating along the inner wall of a cylindrical Space module (Fig. 4a, b) (Antonutto et al. 1991; di Prampero and Antonutto 1996, 1997; di Prampero 2000). The TBS should accomplish two tasks: (1) re-create artificial gravity on board the Space Station and (2) realize a cycloergometric device allowing the two pedalling crew members to perform physical exercise. The two subjects pedalling the TBS generate a centrifugal acceleration ac along their body axis which is given by v2/R, where v is the tangential velocity and R is the radius of the circular motion, equal to the inner radius of the Space module. So, different values of ac can be achieved by appropriately selecting v. The peripheral velocity yielding ac=1 g at the feet level is 4.5 mÆs)1, for a radius of rotation of 2 m, i.e. equal to that of a conventional Space module (Antonutto et al. 1991). The corresponding mechanical (w, W) and metabolic (V_O2, l O2Æmin)1) powers amount to 75 W and 1.2 l O2Æmin)1. Obviously, if R changes (e.g. from 2 to 6 m) the velocity yielding ac=1 g at the feet level will increase to 7.7 mÆs)1, the corresponding mechanical and metabolic powers amounting to 240 W and 3.05 l O2Æmin)1, respectively. The mechanical and metabolic powers needed to develop a given peripheral speed and the related centrifugal acceleration depend on the air density (and hence barometric pressure and temperature)

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Fig. 4a, b Schematic view of the Twin Bikes System. a Cyclists moving along the inner wall of a cylindrically shaped Space module generate an acceleration vector that mimics gravity. b To avoid counter-rotation of the Space module, two cyclists move at the very same speed, but in opposite sense, coupled by a differential gear (drawn on a larger scale). Two adjustable masses prevent the repetitive yaws that would otherwise occur when the two bicycle are on the same side of the Space module. The wheels run on parallel rails providing the initial friction. Thick lines indicate Space module walls. (From Antonutto et al. 1991; di Prampero 2000, with permission)

prevailing inside the Space module and, to a lesser extent, on the friction between the wheels and the rail. It should also be noted that, when riding the TBS, the head of the cyclists will be closer to the rotation centre, as compared to the feet. Consequently, a head-to-feet acceleration gradient will be established along the body axis of the pedalling subjects. The ratio of ac at the feet to ac at the head will be equal to 5 for R=2 m and 1.5 for R=6 m. The above values have been calculated for a subject riding a normal bicycle with upright torso at PB=760 mmHg, T=293K and for a rolling resistance applying to a knobbly-tyred bicycle moving on a concrete surface on Earth (Capelli et al. 1993; di Prampero 2000). Because of the biomechanics and ergonomy of TBS, the centrifugal force due to the mass of the upper part of the subjects’ bodies will be supported by the frames of the bicycles. In contrast, the lower limbs will only sustain a force equal to their own mass times ac. Therefore, whereas the spine will support the upper part of the body, as is the case on Earth, femurs and tibiae will be mechanically stimulated to a lesser extent, i.e. only by their own weight and by the forces generated by

the muscle action during pedalling, a fact which will somewhat reduce the effectiveness of the TBS in counteracting bone demineralization due to microgravity. At variance with the above state of affairs, the TBS ought to be much more effective in protecting against CVD because the weight of the blood column induced by ac will act, as is the case on Earth, throughout the circulatory system. On Earth, the hydrostatic component DP of the arterial pressure is given by DP=qÆgÆh, where q is the blood density, g the acceleration of gravity and h the vertical distance between the left ventricle and the point in question. Therefore, at any level in the circulatory system, the prevailing pressure is given by the sum of the pressure generated by the heart plus (or minus) the hydrostatic component DP. On board the Space module, when riding the TBS, DP will be equal to qÆacÆh. Therefore, since at a given tangential velocity (v), ac increases from head to feet, DP depends on the level considered because of two reasons: (1) the geometrical term h and (2) the local ac value itself depending on the radius of gyration (R). Indeed, for a given v, the angular velocity x (radÆs)1) is also constant, and since v=xÆR and ac=v2ÆR)1, it follows that ac=x2ÆR. The average ac between any two points at distances R1 and R2 from the centre of gyration is given by:   ac ¼ x2  ðR1 þ R2 Þ =2 The hydrostatic pressure gradient between the two points can be therefore calculated substituting h with (R2)R1):   DP ¼ q  x2  ðR1 þ R2 Þ =2  ðR2  R1 Þ Taking R2 at heart level, this equation permits us to calculate the arterial pressure at any given point in the circulatory system, provided that the pressure at heart level is known. For ac=1 g at the subject’s feet and an average pressure of 100 mmHg at the aortic bulbus, the average arterial pressures at the head and feet levels will be 95 and 150 mmHg, if R=2 m and 80 and 170 mmHg, if R=6 m. Slight head movements during cycling on the TBS may lead to vestibular disturbances due to the Coriolis cross-coupled angular acceleration generated by the simultaneous rotation about more of one axis of the semicircular canals. According to Benson (1988), the cross-coupled stimulation of two canals and the resulting sensorial conflict are the major determinants of acute motion sickness (AMS). To test the capability of TBS to induce AMS a model of the TBS has been realized on Earth utilizing the human centrifuge located in the Karolinska Institutet of Stockholm (S) (Antonutto et al. 1993). This model has been utilized by six healthy males who pedalled on a cycloergometer inclined 45 and fixed to the arm of the centrifuge at 2.2 m from the rotation centre, essentially equal to the radius of a conventional Space station module. Since ac=x2ÆR, the centrifuge rotation rate to

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yield ac=1 g at the inner ear level of the pedalling subject was 21 RPM. The sum of ac with the Earth gravity resulted in a vector of 1.41 g applied at the subject’s inner ear and aligned along their body axis. All subjects pedalled for at least 20 min at 50 W during centrifuge rotation. To assess their susceptibility to AMS the six subjects were asked to move their heads according to a protocol involving various degrees of rolling, pitching and yawing. Movements were repeated with open and closed eyes. Only one subject out of six suffered mild AMS (score 3, out of a maximum of 16 according the AMS evaluation protocol proposed by Lackner and Graybiel 1986), corresponding to a subjective definition of ‘‘moderate malaise’’. The symptoms worsened with eyes opened but they disappeared rapidly after the end of the runs. This confirms that the discomfort deriving from the rotating environment necessary to generate artificial gravity is reasonably low and well tolerated. Considering that TBS does not need any external power, being operated by the spacecrews themselves, and that a gravity threshold lower that 1 g is considered sufficient to reduce microgravity deconditioning during long-term Space flights (Keller et al. 1992), we strongly endorse further studies on the possibility of practically realizing the TBS system. Acknowledgement Part of the data reported in this study have been collected thanks to the financial support of the Italian Space Agency (A.S.I.).

References Antonutto G, Capelli C, di Prampero PE (1991) Pedalling in Space as a countermeasure to microgravity deconditioning. Microgravity Q 1:93–101 Antonutto G, Linnasson D, di Prampero PE (1993) On Earth evaluation of neurovestibular tolerance to centrifuge simulated artificial gravity in humans. Physiologist 36 [Suppl. 1]:S85–S87 Antonutto G, Girardis M, Tuniz D, Petri E, Capelli C (1994) Assessment of cardiac output from noninvasive determination of arterial pressure profile in subjects at rest. Eur J Appl Physiol 69:183–188 Antonutto G, Girardis M, Tuniz D, di Prampero PE (1995) Noninvasive assessment of cardiac output from arterial pressure profiles during exercise. Eur J Appl Physiol 72:18–24 Antonutto G, Capelli C, Girardis M, Zamparo P, di Prampero PE (1999) Effects of microgravity on maximal power of lower limbs during very short efforts in humans. J Appl Physiol 86:85–92 Benson AJ (1988) Motion sickness. In: Ernsting J, King P (eds) Aviation medicine. Butterworth, London, pp 318–338 Bungo MW, Johnson PC Jr (1983) Cardiovascular examinations and observations of deconditioning during Space Shuttle Orbital Flight Test Program. Aviat Space Environ Med 54:1001–1004 Bungo MW, Goldwater DJ, Popp RL, Sandler H (1987) Echocardiographic evaluation of Space Shuttle crewmembers. J Appl Physiol 62:278–283 Burton RR (1997) Artificial gravity in Space flight. J Gravit Physiol 4:P17–P20 Burton RR, Meeker LJ (1994) Taking gravity to Space. J Gravit Physiol 1:P15–P18 Capelli C, Rosa G, Butti F, Ferretti G, Veicsteinas A, di Prampero PE (1993) Energy cost and efficiency of riding aerodynamic bicycles. Eur J Appl Physiol 67:144–149

Cardu`s D (1994) Artificial gravity in space and in medical research. J Gravit Physiol 1:P19–P22 Cautero M, Antonutto G, Fusi S, Tam E, di Prampero PE, Linnarsson D, Ferretti G, Capelli C (2003) Oxygen uptake at the onset of step-exercise before and after short duration bed rest in humans. J Gravit Physiol (in press) Charles JB, Lathers CM (1991) Cardiovascular adaptation to spaceflight. J Clin Pharmacol 31:1001–1023 Charles JB, Bungo MW, Fortner GW (1994) Cardiopulmonary function. In: Nicogossian AE, Leach Huntoon C, Pool SM (eds) Space physiology and medicine. Lea and Febiger, Philadelphia, pp 286–304 Churchill SE, Bungo MW (1997) Response of the cardiovascular system to spaceflight. In: Churchill SE (ed) Fundamentals of space life sciences, vol 1. Krieger, Malabar Fla., pp 41–63 Fahri LE, Nesarajah MS, Olszowka AJ, Metildi LA, Ellis AK (1976) Cardiac output determination by a simple one step rebreathing technique. Respir Physiol 28:141–159 Ferretti G, Girardis M, Moia C, Antonutto G (1998) Effects of prolonged bed rest on cardiovascular oxygen transport during submaximal exercise in humans. Eur J Appl Physiol 78:398–402 Ferretti G, Berg HE, Minetti AE, Moia C, Rampichini S, Narici MV (2000) Maximal instantaneous muscular power after prolonged bed rest in humans. J Appl Physiol 90:431–435 Fortney SM, Schneider VS, Greenleaf JE (1996) The physiology of bed rest. In: Fregly MJ, Blatteis CM (eds) Handbook of physiology, section 4, vol 2. Environmental physiology. American Physiological Society, Bethesda, Md. and Oxford University Press, Oxford, pp 889–939 Fritsch JM, Charles JB, Bennett BS, Jones MM, Eckberg DL (1992) Short-duration space flight impairs human carotid baroreceptor-cardiac reflex responses. J Appl Physiol 73:664– 671 Gazenko OG, Schilzenko EB, Yegorov AD (1985) Cardiovascular changes in prolonged spaceflights. IAF Preprint, 36th IAF Conference, Stockholm (S). Pergamon, New York Greenleaf JE, Gundo DP, Watenpaugh DE, Mulenburg GM, McKenzie MA, Looft-Wilson R, Hargens AR (1997) Cyclepowered short radius (1.9 m) centrifuge: effect of exercise versus passive acceleration on heart rate in humans. NASA Technical Memorandum 110433 Hall TW (1994) The architecture of artificial-gravity environments for long-duration space habitation. Doctoral dissertation, University of Michigan, UMI, Ann Arbor Hastreiter D, Young LR (1997) Effects of gravity gradient on human cardiovascular responses. J Gravit Physiol 4:P23–P26 Henry WL, Epstein SE, Griffith LM, Goldstein RE, Redwood DR (1977) Effect of prolonged space flight on cardiac function and dimension. In: Johnston RS, Dietlein LF (eds) Biomedical results from Skylab (NASA SP-377). US Government Printing Office, Washington DC, pp 366–371 Hinghofer-Szalkay HC (1996) Physiology of cardiovascular, respiratory, interstitial, endocrine, immune and muscular systems. In: Moore D, Bie P, Oser H (eds) Biological and medical research in Space. Springer, Berlin Heidelberg New York, pp 107–153 Hoffler GW, Bergmen SA, Nicogossian AE (1977) In-flight lower limb measurement. In: Nicogossian AE (ed) The Apollo–Soyuz Test Project medical report (NASA SP-411). US Government Printing Office, Washington DC, pp 63–68 Johnson RL, Driscoll TB, Le Balnc AD (1977) Blood volume changes. In: Johnston RS, Dietlein LF (eds) Biomedical results from Skylab (NASA SP-377). US Government Printing Office, Washington DC, pp 284–312 Keller TS, Strauss AM, Szpalsky M (1992) Prevention of bone loss and muscle atrophy during manned space flight. Microgravity Q 2:89–102 Lackner JR, Graybiel A (1986) The effective intensity of Coriolis cross-coupling stimulation is gravitoinertial force dependent: implication for space motion sickness. Aviat Space Environ Med 57:229–235

291 Lane HW, Alfrey CP, Driscoll TB, Smith SM, Nyquist LE (1996) Control of red blood cell mass during space flight. J Gravit Physiol, 3:87–90 Leach CS, Rambaut PC (1977) Biochemical responses of the Skylab crewmen: an overview. In: Johnston RS, Dietlein LF (eds) Biomedical results from Skylab (NASA SP-377). US Government Printing Office, Washington DC, pp 204–216 Leach CS, Inners LD, Charles JB (1991) Changes in total body water during spaceflight. J Clin Pharmacol 31:1001–1006 Leach Huntoon CL, Cintro`n NM, Whitson PA (1994) Endocrine and biochemical functions. In: Nicogossian AE, Leach Huntoon C, Pool SM (eds) Space physiology and medicine. Lea and Febiger, Philadelphia, pp 334–350 Linnarsson D, Sundberg CJ, Tedner B, Haruna Y, Karemaker JM, Antonutto G, di Prampero PE (1996) Blood pressure and heart rate response to sudden changes of gravity during exercise. Am J Physiol 270:H2132–H2142 Minetti AE (2002) On the mechanical power of joint extensions as affected by the change in muscle force (or cross sectional area), ceteris paribus. Eur J Appl Physiol 86:363–369 Nicogossian AE, Pool SM, JJ Uri (1994) Historical perspectives. In: Nicogossian AE, Leach Huntoon C, Pool SM (eds) Space physiology and medicine. Lea and Febiger, Philadelphia, pp 3–49 di Prampero PE (2000) Cycling on Earth, in space, on the Moon. Eur J Appl Phisiol 82:345–360 di Prampero PE, Antonutto G (1996) Effects of microgravity on muscle power: some possible countermeasures. In: ESA Symposium Proceeding on ‘‘Space Station Utilization’’, Darmstadt, ESA-SP-385, pp 103–106 di Prampero PE, Antonutto G (1997) Cycling in Space to simulate gravity. Int J Sports Med 18:S324–S326 di Prampero PE, Narici MV (2003) Muscles in microgravity: from fibres to human motion. J Biomech 36:403–412

Rowell LB (1986) Human circulation. Regulation during physical stress. Oxford University Press, New York, pp 137–173 Spaak J, Sundblad P, Linnarsson D (2001) Impaired pressor response after spaceflight and bed rest: evidence for cardiovascular dysfunction. Eur J Appl Physiol 85:49–55 Sundblad P, Spaak J, Linnarsson D (2000) Cardiovascular response to upright and supine exercise in humans after 6 weeks of head-down tilt ()6 degrees). Eur J Appl Physiol 83:303–309 Vernikos J (1997) Artificial gravity intermittent centrifugation as a space flight countermeasure. J Gravit Physiol 4:P13–P16 Vil-Viliams IF, Kotovskaya AR, Shipov AA (1997) Biomedical aspects of artificial gravity. J Gravit Physiol 4:P27–P28 White WJ (1965) Space-based centrifuge. Proceedings of 1st Symposium on the Role of the Vestibular Organs in the Exploration of Space. U.S. Naval School of Aviation Medicine, Pensacola, Fla., and NASA, Washington DC, pp 209–213 Yegorov AD, Alferova IV, Polyakiva AP (1988a) State of cardiodynamics under conditions of long-term weightlessness. Kosm Biol Aviakosm Med 22:4–7 Yegorov AD, Itsekhovskiy OG, Alferova IV, Turchaninova VF, Polenova AP, Golubchikova ZA, Domracheva MV, Lyamin VR, Turbasov VD (1988b) Study of cardiovascular system of Salyut-6 prime crew. USSR Space Life Digest 14:18–19 Zamparo P, Minetti AE, di Prampero PE (2002) Interplay among the changes of muscle strength, cross-sectional area and maximal explosive power: theory and facts. Eur J Appl Physiol 88:193–202 Zange J, Mueller K, Schuber M, Wackerhage H, Hoffmann U, Guenther RW, Adam G, Neuerburg JM, Sinitsyn VE, Bacharev AO, Belichenko OI (1997) Changes in calf muscle performance, energy metabolism and muscle volume caused by long term stay on space station MIR. Int J Sports Med 18 [Suppl. 4]:S308– S309