The maintenance of physiological function in humans during spaceflight

Centre National de le Recherche Scientifique, Centre de Recherche Cerveau et Cognition, UMR 5549 CNRS-UPS, Faculté de Médecine Rangueil, Toulouse, France

Objective: There are a number of physiological changes which occur in astronauts in both short- and long-duration space missions, including nausea and spatial disorientation, orthostatic hypotension, muscle atrophy, bone loss, increased cancer risk from space radiation, and many others. This review examines the procedures and methods, also called countermeasures, used to moderate these changes. Data sources: The information in this paper is taken from a review of articles and book chapters (Source: PubMed and MEDLINE, years covered 1995-2005). Conclusions: The countermeasures currently adopted to counteract the effects of microgravity conditions on board space missions aim at stimulating a particular physiological system: the treadmill, the cycle ergometer and the interim resistive exercise device primarily for muscles and bones, intermittent venous pooling and fluid loading for cardiovascular responses, and pharmacological manipulations for space motion sickness. However, all have only limited success. Indeed, despite extensive in-flight exercise, most astronauts experience difficulties in standing, walking and getting oriented for several days after landing. This poses a serious problem in case of an emergency landing on Earth or a landing on Mars after a long-duration spaceflight. Studies are being conducted for the search of more effective countermeasures that address all physiological systems across the board, such as artificial gravity generated by short-arm centrifugation. Keywords: spaceflight, de-conditioning, heart, muscle, bone, exercise, countermeasure, microgravity

Exposure to microgravity and the space environment during short- and long-duration space missions has important medical and health implications in astronauts. These include neurovestibular problems involving space motion sickness and disorientation during the flight ^1,2, and impaired balance and neuromuscular coordination after landing ^3,4; cardiovascular and fluid-related problems of orthostatic hypotension immediately following spaceflight ^5,6; the possibility of altered cardiac susceptibility to ventricular arrhythmias ⁷, and reduced cardiac muscle mass and diminished cardiac function ⁸; muscle-related problems of atrophy involving loss of muscle mass, strength and endurance ^9,10; decrease in the bone mineral density ^11,12; circadian rhythm-related problems involving sleep and performance ¹³; and immune-related problems involving infections and immunodeficiency ¹⁴. Numerous countermeasures have been developed and tested for moderating these physiological changes. Some procedures are utilised before the flight, such as screening and selecting new astronaut candidates; others are utilised during the flight, such as the administration of drug or exercise regimens, or after the flight for a prompt return of crew members to flight status ¹⁵. In this paper, the procedures and methods currently used for alleviating the physiological changes noted in major body systems during adaptation to microgravity are reviewed. A brief review of the countermeasures currently tested for planetary exploration missions, such as long-duration missions to the Moon or Mars, is also provided.

Original research articles, review articles, book chapters and reports relevant to the maintenance of major body functions in astronauts before, during and after spaceflight were reviewed. Discussion of the countermeasures used for each of these functions during the various phases of the flight is provided.

Countermeasures refer to the application of procedures or therapeutic (physical, chemical, biological, or psychological) means to maintain physiological balance, health, physical fitness, and mission performance; reduce risk; and improve the safety of human spaceflight. The countermeasures typically aim at preventing, mitigating, or minimising the effect of adverse or harmful agents on the crew ¹⁶.

Before the flight, countermeasures include those activities which support crew selection and physiological training, fitness and exercise, health stabilisation programme, and circadian shifting. Based on the knowledge of specific health risk factors associated with spaceflight, appropriate and proven tests are utilised in selecting the astronauts. After selection, annual medical evaluations are performed to identify and correct medical risks to maintain health, provide certification for flight duties, and ensure career longevity. These tests include further clinical evaluation and fitness assessments in order to prescribe individualised exercise programmes and provide customised pre-flight and post-flight conditioning activities. The purpose of the Crew Health Stabilisation programme is to prevent flight crews from exposure to contagious illness just before launch. A pre-flight quarantine limits access to flight crew during the seven days just prior to launch. Even before this period, the health of an active duty crew member family is of critical importance, because factors such as infectious disease and stress affecting a crew member family may have serious adverse effects on the crew member health and performance, as well as the health and performance of other crew members. Medical and dental care is provided by an on-site flight medical clinic to the crew member’s immediate family ¹⁶.

During the flight, among the potential health risks are the levels of acceleration, vibration, and noise during launch, the exposure to toxic substances and pressure changes, and the risk due to radiation. Extra-vehicular activity (spacewalks) can also be responsible for strain on muscles and bones, and decompression-related disorders. In addition, there are a number of physiological changes which occur in astronauts in both short- and long-duration space missions. With the possible exception of the immune system, body changes that occur after entering microgravity represent normal homeostatic responses to a new environment. The body’s control systems recognise the lack of gravity and begin to adapt to this unique situation, not realising that the ultimate plan is to return to normal gravity after a transient visit to microgravity. In-flight, typical adaptive and pathophysiological changes occur in the neurovestibular system (space motion sickness), cardiovascular system (fluid loss, decrease in cardiac function, dysrhythmias), and the musculoskeletal systems (muscle atrophy and bone mineral loss) ¹⁶.

During the return to Earth, piloting tasks are challenged by the presence of g forces in de-conditioned individuals. After nominal landing, astronauts often exhibit post-flight orthostatic intolerance, as well as a decrease in aerobic capacity and difficulties in standing and walking. Impairment in eye-head coordination, nausea and spatial disorientation are also present. These difficulties could prove dramatic in the case of a non-nominal landing where the crew may be required to egress in an emergency vehicle with no help from ground support ¹⁶.

After landing, health monitoring and physical rehabilitation are performed to accelerate the return of crew members to normal Earth-based duties. Post-flight countermeasures include those activities necessary to assist the crew members in a return to physical, physiological, and behavioural health baselines. An important factor to take into account is the return to flight status for pilot astronauts. Examples of countermeasures include, but are not limited to, circadian rhythm shifting, hormone replacement, and physical exercise. Longitudinal studies of astronaut health are also conducted to investigate whether the unique occupational exposures of astronauts are associated with increased health risks. Such studies are particularly relevant regarding the issues of radiation exposure ¹⁶.

Space motion sickness is a very common yet poorly understood and debilitating syndrome of sweating, dizziness, nausea and vomiting that affects about two-thirds of all astronauts during the first two days of flight. Critical activities, such as space walks, manual docking with other spacecraft, or landing, are not scheduled during this period for just this reason. Preventive training techniques, such as exposures to sensory conflicts ¹⁷, or sensory stimulus rearrangement ¹⁸, or the combined application of biofeedback and learned self-regulation technique ¹⁹, have been used in the past with limited success. In addition, since there is no correlation between susceptibility to motion sickness in the ground-based tests and susceptibility to space motion sickness ²⁰, these time-consuming procedures may not be necessary in all individuals.

Intramuscular injection of antihistamine promethazine has been quite successful, decreasing the symptoms of space motion sickness in most, but not all, crew members. Recent research indicates, however, that this medication can cause deleterious side effects that further degrades human performance and negatively impacts mood and sleep ²¹.

Orthostatic intolerance is characterised by a variety of symptoms that follow standing after landing: light-headedness, increase in heart rate, altered blood pressure, and pre-syncope or syncope. These symptoms are often accompanied by diminished exercise capacity. Orthostatic intolerance and diminished exercise capacity become more severe with longer exposure to microgravity and require more lengthy recovery times after returning to Earth ⁶. It is now well accepted that the post-flight orthostatic intolerance is due to more than just loss of fluid during spaceflight. It is presumably caused by three related factors: the volume of blood in the blood vessels, the ability of blood vessels to expand or constrict to maintain blood pressure, and the functioning of the heart itself ²². Indeed, numerous irregularities of heart rhythm have been noted during spaceflights, mostly during spacewalks, intense exercise activity or during re-entry ⁵.

Because the cardiovascular de-conditioning associated with spaceflight is due to multiple causes, four or five different countermeasures in some combination are needed to solve the problem completely. One of these countermeasures is compensating for the loss of fluid by ingesting about one litre of water or juice and eight salt tablets about 1 hour before leaving orbit. This fluid loading protocol produces one litre of isotonic saline in the digestive track, which then leads to absorption and subsequent increase in plasma volume. This technique proved effective for short-duration missions by reducing the occurrence or severity of post-flight orthostatic intolerance. However, the effectiveness of fluid loading is reduced with longer time in orbit ²³. It is suspected that factors other than cardiovascular de-conditioning become more important on longer flights with regard to causing orthostatic intolerance ⁵.

A lower body negative pressure (LBNP) is a device that can be used by the end of a mission for predicting which astronauts will be more susceptible to post-flight orthostatic intolerance (Figure 1). This device provides a rapid decompression from ambient pressure to -60 mm Hg and therefore similar effects to post-flight orthostatic intolerance can occur. Slower or constant decompression regimes can then be applied to recondition the system for Earth's gravity. There are, however, significant inter- and intra-individual differences in the responses to in-flight LBNP tests, which make it difficult to use as a predictive tool ²⁴.

Figure 1: Astronaut showing the Lower Body Negative Pressure device used on the International Space Station. The device encloses the lower abdomen and lower extremities to maintain a controlled pressure differential below ambient. This causes the intravascular blood volume to shift towards the lower extremities in microgravity, in a manner similar to the orthostatic load caused by assuming an upright posture in Earth gravity. Photo: NASA

In the critical period of re-entry and landing, Shuttle astronauts routinely may wear anti-gravity suits. These suits contain balloon-like pressure bladders in the pants, which can be inflated with air by the astronaut. When the astronaut inflates the bladders in his or her pants, the bladder presses against the legs, forcing body fluid into the upper body. This helps the heart to pump the blood more efficiently by pushing the blood out of the lower extremities. The Russians wrap the lower body tightly with elastic strapping to achieve the same effect as the anti-gravity suit.

Anyone who has been on orbit for more than 30 days is required to be returned to Earth in the supine position (+Gx acceleration) to reduce the risk of orthostatic intolerance during re-entry and landing. The Space Shuttle is equipped with recumbent seats for returning long-duration crew members from the ISS (Figure 2). There is, however, a concern that a long-duration flight crewmember could probably not egress from the recumbent seat system without some assistance.

Figure 2: This photograph of the mid-deck of the Space Shuttle configured for return to Earth shows the three ISS crew members in their recumbent seats (right) by comparison with the upright seat of the Shuttle crew members (left). Photo: NASA

Although its effects on orthostatic tolerance are still unknown, the in-flight aerobic exercise programme which is done in conjunction with the exercise for counteracting muscle atrophy (see below), seems to be partially effective in maintaining post-flight aerobic capacity. The Space Shuttle crews exercise once every second day after being in orbit for more than three days ²⁵. More stringent daily physical exercise is scheduled for the International Space Station (ISS) crew members, which involves three exercise periods of 2.5 hours per day for three days, with some optional change on the fourth day. Special restraint systems (e.g. bungee cords) are required to hold the astronauts in place during exercise sessions. While exercising, the Russian cosmonauts sometimes also use thigh constriction cuffs to decrease fluid shift, although real data on the effectiveness of these cuffs are lacking ⁸. Further in-flight countermeasures include whole-body elastic loading suits, such as the Russian “Penguin” suit (Figure 3).

Figure 3: The “Penguin” suit. The inside of the suit contains a system of elastic, straps, and buckles that can be used to adjust the fit and tension of the suit. This suit forces the subjects to use his extensor muscles in-flight to activate venous return. Drawing by Philippe Tauzin.

After only five days in space, muscle atrophy begins and the urinary excretion of nitrogen compounds increases ¹⁰. Astronauts lose 10-20% of their muscle mass on short missions. It has not been determined whether muscle deterioration reaches a plateau during long-duration spaceflight. This atrophy is characterised by both structural and functional alterations. There is a decrease in muscle fibre size, with no apparent change in fibre number. Atrophy is considerably greater for the postural muscles, i.e. those muscles that support activities such as walking, lifting objects, and standing on Earth, as compared to the non-postural muscles, which undergo only marginal changes. On long-duration flights, the muscle loss might rise to 50% without using countermeasures. In addition to pure muscle loss, the fibres involved in muscle contractions change their contractile properties and are weakened ²⁶. The associated continued excretion of nitrogen may also have deleterious hormonal and nutritional effects. Losses have also been found in muscular stamina and contractile endurance ⁹.

Several exercise devices are available on the ISS for exercise, including a treadmill to preserve aerobic power, a cycle ergometer to preserve aerobic capacity, a resistive exercise device to preserve muscle strength, and hand grip equipment to preserve hand strength for extra-vehicular activity. This is a unique suite of exercise equipment designed for operating in microgravity and taking into account the constraints imposed by space missions, such as minimal size, volume, weight, power consumption, and maintenance.

Figure 4: Astronaut equipped with a bungee harness and exercising on the treadmill on board the International Space Station. A vibration isolation system reduces the vibration transferred from the treadmill to the Station’s structure during exercise. Photo: NASA.

The treadmill may be used for walking, running, and doing knee bends and resistive exercise (Figure 4). Loads are exerted on the subject by restraint harnesses to simulate, as closely as possible, normal gravity skeletal loading during exercise. There are two modes of operation: the motorised (active) mode provides astronauts with speed control adjustable from 0-16 km/h; the non-motorised mode allows the astronaut to drive the tread belt with variable mechanical resistance without the use of a motor. The treadmill can be used as an ambulating trainer, endurance exercise of postural musculature, high impact skeletal loading (bone maintenance), and aerobic exercise.

Figure 5: Astronaut on the International Space Station exercising on the cycle ergometer. Photo: NASA

The cycle ergometer provides workload variable between 25 and 350 watts, driven by the hands or feet, which is controlled by manual or computer adjustment (Figure 5). It operates with the subject seated or supine, and provides time-synchronized data compatible with other complementary analyses. The cycle ergometer is used as an aerobic and anaerobic exercise countermeasure, for the maintenance of lower body musculature endurance and for arm exercise training in preparation for extravehicular activity

Figure 6: Left: Astronaut wearing squat harness pads, performs knee-bends using the Interim Resistive Exercise Device (IRED) equipment on board the International Space Station. Right: He is using the "short bar" of the IRED to perform upper body strengthening pull-ups. Photo: NASA

The Interim Resistive Exercise Device (IRED) includes a series of human-machine interface devices (e.g. handgrips, straps, curl bars, ankle cuffs, squat harness, etc.) that permit a variety of exercises to be performed by the astronauts (Figure 6). Cables on each side of shoulder straps are connected to two canisters, each containing a series of “flex packs” that can be dialled in sequentially to add greater resistance to the cables. The device provides eccentric and concentric contraction through a full range of motion of various exercises (Table 1). The IRED is used as training for muscle strength and endurance of all major muscle groups, to maintain skeletal muscle mass and volume, and to provide high-strain skeletal loading (bone maintenance, see below).

Table 1: Resistive exercise workout recommended daily for the ISS astronauts. Note that lower body exercises are performed every day.

Day 1

Deadlifts

Bent-over rows

Straight leg deadlifts

Heel raises

Day 2

Shoulder presses

Rear raises

Front raises

Hip abduction

Hip adduction

Day 3

Squats

Heel raises

Straight leg deadlifts

Bent-over rows

As seen above, Russian cosmonauts wear the “Penguin” suit during long-duration missions (Figure 3). Besides its effect on the cardiovascular system, the elastic bands in the suit also simulate some of the gravitational effects on the musculoskeletal system. Expanders are also used occasionally. However, they do not provide sufficient force during axial loading for bone maintenance, and present a reduced range of motion against resistance compared to the interim resistance exercise device described above.

Bone loss during spaceflight is about 1-2% per month. The effect is especially marked in the weight-bearing bones of the legs and spine. Certain individuals on six-month flights have lost as much as 20% of bone mass throughout their lower extremities while maintaining upper body bone mineral density ¹¹. There is no indication that this bone loss abates with longer flights. Furthermore, after return to Earth, bone loss continues for several months ¹². Bones lose calcium, the mineral from which they derive their structure and strength, through the process of demineralisation. This increased excretion of calcium may in turn affect various organs, especially the kidneys, and increase the risk of renal stone formation, which could have serious consequences during a mission. In addition to demineralisation, changes in bone marrow have also been linked to bone loss ²⁷.

Despite the intensive exercise schedules described above, astronauts continue to lose bone selectively from the spine and lower extremities. Correlative observations have indicated that the required procedure for use of a mechanical countermeasure in flight should provide the equivalent force on the skeleton of four hours of walking per day ²⁸.

Among the nutritional countermeasures tested have been a high calcium and high phosphorus intake by astronauts. The study showed that this procedure maintained a balanced calcium intake and excretion level for up to three months, following which the gradually rising faecal excretion of calcium again caused a negative calcium balance ²⁹.

Astronauts regularly perform weight-loading exercises that simulate the gravity of Earth. However, exercise alone has not prevented muscle and bone loss during spaceflight. Different types of exercise are required to build muscle strength and resistance to fatigue and injury, and maintain bone integrity. Studies continue to be conducted to address how muscles and bones should be loaded in microgravity in order to prevent these changes.

Some scientists currently believe that bone mass is not only controlled by the high-magnitude, low-frequency strain resulting from the mechanical loads on bones associated with vigorous exercise, but also by low-magnitude and high-frequency strain that the musculature continuously places on bones while sitting or standing. Results of ground-based studies suggest that barely perceptible vibrations may generate enough strain to stimulate bone growth ³⁰. If proven valuable for humans, low-level vibrations during spaceflight may offer an alternative for the current, time-consuming astronaut exercise regimes for long-duration space missions.

Other countermeasure projects are attempting to increase protein synthesis rates with supplements of amino acids for muscle. For bone, studies are looking at bisphosphonate compounds that bind to bone crystal and tend to inhibit bone resorption ³¹, or the hormone glucose-dependent insulino-tropic peptide, which is involved in insulin production that some bone cells contain. Obviously, a balance between healthy nutrition, therapeutic measures, drugs, and exercise is likely to be the most effective countermeasure ^32,33.

Artificial gravity represents a different approach to the problem of microgravity effects on the human body, as it simply mimics our natural 1-g environment. Not just one physiological system at a time is challenged by artificial gravity, but all systems simultaneously: bone stress, anti-gravity muscles, vestibular organs, and cardiovascular apparatus ³⁴. It is very likely that humans do not need gravity, or a fraction of it, 24-hours a day to remain healthy. If intermittent gravity is sufficient, a permanently rotating spacecraft would not be needed to produce a constant gravity force ³⁵. Instead an onboard human short-arm centrifuge presents a realistic near-term opportunity for providing artificial gravity ³⁶. The validation of short-arm centrifugation is presently evaluated during bed rest studies ³⁷(Figure 7).

Figure 7: The short-radius centrifuge used at NASA, Wyle Laboratories and University of Texas to conduct physiological studies aimed at validating the effects of centrifugation as a countermeasure during bed rest. Cover of the 25 April, 2005 issue of Aviation Week & Space Technology. Photo by Peter Rogers.

Despite the use of in-flight countermeasures, orthostatic intolerance remains a major, unresolved, clinical and operational problem ²². After a three-month stay on board the ISS, the astronauts and cosmonauts are unable to stand immediately after returning to Earth. They commonly experience nausea and disorientation, and considerable muscle and bone loss is still observed after landing. Much remains to be done to find the best procedure for the use of the physical conditioning procedures, as well as the nutritional and pharmacological procedures, so as to least-impact on the activities conducted aboard the ISS.

Using the current countermeasure methods, humans would not be operational after landing on Mars following a six-month journey in microgravity. With the exception of bone, changes in all the major body functions (neurovestibular, cardiovascular, muscular) are entirely reversible upon return to normal gravity, and there appears to be no deleterious effect of spaceflight directly on the immune system. Might these changes become irreversible after a longer exposure, such as the two-year round trip mission planned for Mars? Is artificial gravity, even partial and intermittent, needed during the flight? Will the Martian gravity (0.38 g) be sufficient for re-adapting these functions while on the Red Planet’s surface? These are just some of the questions that remain to be addressed before humans can be safely sent on such missions.

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ISMJ International SportMed JournalThe maintenance of physiological function in humans during spaceflight

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International SportMed Journal
The maintenance of physiological function in humans during spaceflight