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. | COUNTERMEASURES TO LONG-DURATION SPACEFLIGHT Part Two Tamarack R. Czarnik, MD Resident, Aerospace Medicine – Wright State University
Abstract This two-part paper examines the past, present and experimental countermeasures used to counteract the body’s adaptations to long-duration spaceflight. In Part One, we took a historical overview of our understanding of these adaptations, and examined countermeasures to Space Motion Sickness, Sleep Disturbance and Fluid Redistribution. In this paper, Part Two, we explore countermeasures to Loss of Bone Minerals, Muscle Atrophy, Cardiac Deconditioning, Vestibular Dysfunction and Psychological Asthenia and Stress. Finally, we consider a paradigm shift from relying on countermeasures to accepting a period of ‘pre-adaptation’, and how this might be implemented in Earth Orbit.
Loss of Bone Mineral Density Loss of total body calcium, and specifically loss of calcium in bone (bone mineral density, or BMD), is the change most often referred to as a ‘showstopper’, a reason we cannot mount a piloted Mars mission, and the argument has some merit. Since the early Apollo and Skylab days, we’ve known that the body loses calcium progressively in microgravity. This loss of calcium comes mainly from trabecular (or ‘spongy’) bone; it is resorbed predominantly from weight-bearing areas (no longer under stress in microgravity), and it is lost most in the legs, less in the arms and ribcage. Bone mineral density actually increases at the skull. Furthermore, loss of bone is progressive; the longer you’re up, the more you lose. The risk here is not just from thinning bones; higher levels of free calcium in the body increase the danger of kidney stones and soft tissue calcifications, as well as increasing the likelihood on fractures. These arguments, while strong on the face of them, are not as irrefutable as once thought. Certainly bone loss is progressive, but long-term (> 1 year) studies on-orbit appear to show a plateauing of bone loss; the body seems to reach a new equilibrium, after which bone loss slows. Longer-term studies done using bedrest, cast immobilization and paraplegia to model the bone loss of inactivity confirm that bone loss is not exhaustive; quadriplegics don’t lose ALL their bone, they simply reach a new equilibrium. Astronauts won’t come back from a 3-year trip to Mars as jellyfish, but we shouldn’t expect them to squat 450 pounds either. Countermeasures to bone loss have mainly focused on increased exercise, with disappointing results. One difficulty is inconsistency; some astronauts just lose more bone and retain less with exercise than others, and we have no way of knowing who’s who before flight. Following a flight of several months by two cosmonauts one had lost 10% of vertebral bone density while the other showed no loss at all. Crews of Skylab-3 and –4 exercised heavily and consistently, yet 3 of the 6 showed substantial mineral losses. The newest exercise regimens make use of high-impact stress; while detrimental on Earth, these ‘short, sharp shocks" to the bone and muscle seem to stimulate retention of bony calcium. Use of supplemental dietary calcium and calcium-retaining drugs like Clodronate (used in post-menopausal osteoporosis) have shown some promise, and will be evaluated in upcoming flights. Technical and hardware constraints have hindered the evaluation of Artificial Gravity as a countermeasure to bone loss in humans, but experiments in the Russian Kosmos biosatelittes have shown it prevents calcium and phosphorus loss from rats in microgravity. This suggests that AG would prevent bone loss in humans as well, thus freeing us from this potential ‘showstopper’. Muscle Atrophy Muscle, which constitutes nearly 40% of the body by volume, is also seriously depleted in long-duration microgravity; no longer having to resist the force of gravity, the slow-twitch (oxidative, fatigue-resistant, ‘red meat’) muscles atrophy, necrose and transform to fast-twitch, while the fast-twitch (glycolytic, easily-fatigued, ‘white meat’) muscles are much less affected. Consequently, muscles are weakened, more easily fatigued, reflexes are briefer, and some fine motor control is degraded. Moreover, the rate of atrophy is somewhat greater than that shown in complete bed rest; a 35-day spaceflight can cause as much as a 25% atrophy of leg muscles. The image of Salyut cosmonauts being carried from their craft onto recliners set in the field, apparently unable to walk, occurs to anyone contemplating long-duration spaceflight. In fact, returning cosmonauts were carried out more to preserve postflight data than from muscle weakness. Today, only about one in 10 astronauts cannot stand upright and walk from the Shuttle orbiter without help. Muscle atrophy was foreseen by early Aerospace Medicine specialists, who suggested increased exercise; unfortunately, despite vigorous use of a cycle ergometer, mini-gym and treadmill (with bungee cords to restrain the jogger) on Skylab-4, atrophy and fatigue continued. The ‘Penguin suit’ (flight suit with restraining bungee cords, placed to reproduce muscles’ resistance to gravity), electrical contraction of muscles, passive stretch and anabolic drugs each seem to alleviate some atrophy, but to date no single treatment or protocol has effectively halted muscle wasting. On the other hand, all countermeasures are somewhat effective, and some combinations of protocols work better than others. Exercise that is eccentric (muscle-lengthening, as in the ‘down’ phase of a dumbbell curl) is more effective at preserving muscle mass than concentric (muscle-contracting, as in the ‘up’ phase of the curl) exercise, and thus more eccentric exercises are planned for the International Space Station (ISS) astronauts. Following his spaceflight of greater than a year’s duration, cosmonaut Valeri Polyakov was on his feet and hitting the lecture circuit within 10 days. Prevention of muscle atrophy has been more successful than that of bone loss, and is unlikely to pose a significant threat to long-duration flights. Cardiac Deconditioning In microgravity the blood is ‘weightless’, significantly decreasing the heart’s workload in circulating it. Fluid redistribution (see Adaptations to Long-Duration Spaceflight, AeroMed paper #2 in the series) causes a diuresis, which decreases plasma volume; the body, sensing an increase in blood concentration, stops making red cells, further decreasing the mass of blood to be moved in microgravity. All this means that the heart, like any other muscle, is much less tasked in space, and as a result it gets weaker. In addition, the body’s control of the heart and blood pressure seems to be degraded by long exposure to microgravity. Carotid baroreceptors (pressure sensors in the neck) normally keep pulse and arterial pressure appropriate to maintain perfusion to the brain, but after long spaceflight this control is less responsive, contributing to orthostatic intolerance (dizziness on standing). Abnormal heart rhythms are increased in microgravity (occasionally severely increased), though the mechanism is unclear, and potentially dangerous rhythms have been noted during Gemini, Apollo, Skylab and Shuttle flights. More than their American counterparts, Russian biomedical researchers have favored the use of drugs to counter this deconditioning. Cosmonauts have used nitroglycerine, panangin (potassium, magnesium and asparaginate), riboxin, potassium orotate and a class of drugs called GABA analogues to control cardiac disturbances, with varying success. Russian researchers also use protocols of the ‘Penguin’ suits, Chibis suits (lower-body negative pressure suits) and G-suits with exercise regimens. American aerospace physiologists tend to more favor the proven beneficial effects of aerobic training while on orbit, and hours are spent daily on the treadmill and cycle ergometer. Potassium dietary supplements have been used since cardiac arrhythmias in the long postflight recovery following Apollo 15 were linked to low dietary potassium, and seem to have prevented recurrences. Saline loading before re-entry (discussed in Countermeasures Part One) helps but does not prevent postflight orthostatic intolerance. But cardiac dysrhythmias and a loss in postflight aerobic conditioning persist, and research into more effective countermeasures will continue. Vestibular Disorientation As discussed in Adaptations to Spaceflight (AeroMed paper #1), microgravity causes a loss of the normal functioning of the vestibular (‘balance’) apparatus in the inner ear. Otoliths (tiny stones at the end of hair cells in the inner ear) no longer bend the hair cells in response to gravity, so the body loses its ‘innate’ sense of up and down. Since the body has adapted to integrate visual and vestibular inputs to figure out what’s going on, such vestibular dysfunction frequently causes ‘visuo-vestibular mismatch’: the eyes see one motion, the ear ‘feels’ another, the brain gets confused and the stomach rebels. Overall, 40 – 40% of astronauts and cosmonauts experience in-flight vestibular disorientation, including sensations of tumbling or rotation, vertigo or postural illusions. Interestingly, after a 2 – 7 day adaptation period, the astronaut’s body seems to adapt to the new set of stimuli. Provocative motion stimuli (sensations that tend to make people nauseous) lose their effect, and this immunity to provocative stimuli persists for several days postflight: astronauts immediately postflight don’t get sick on the KC-135 (the airplane that simulates microgravity by flying parabolas; also known as the ‘Vomit Comet’) as frequently. Some cosmonauts on very long duration stays in microgravity have reported reappearance of illusions later in the flight. On return to 1 G, the body’s new adaptation again takes several days to ‘reorient’. Imagine astronauts newly returned to Earth, trying to escape noxious fumes in their Soyuz or Crew Rescue Vehicle, unable to orient to ‘up’ and ‘down’, much less find the escape hatch. It is this prospect, of a weakened, nauseous, dehydrated and disoriented astronaut trying vainly to escape their burning vehicle that keeps aerospace physiologists up at night. Though no effective countermeasures to this disorientation have yet been found, some encouraging findings are noted. Studies on the recent Neurolab mission indicate that some astronauts tend to maintain and image of ‘up and down’ along their body axis; this would tend to make reorientation easier. Some improvement of postflight disorientation has been noted with saline ingestion. Investigation into the causes and treatment of postflight disorientation continue. Psychological Asthenia and Stresses The term ‘asthenia’ refers to lassitude, or an enervated, lethargic and apathetic emotional state, and is rarely seem in the American literature. But Russian space docs, with decades of experience in the consequences of long-duration spaceflight on Salyut and Mir, have noted increasing problems as mission got longer. As discussed in Adaptations to Long Duration Spaceflight (AeroMed paper #1), the middle phase on a long spaceflight is marked by increasing fatigue and loss of motivation, irritability and emotional lability; if countermeasures are not instituted, a final ‘long-duration’ stage of hypoactivity, feelings of isolation and worsened asthenia proceeds. Sleep is prolonged and disturbed, depression and hostility worse, and productivity plummets. While not well-reported in the literature (due in part to avoidance of negative publicity), examples of this behavior abound. During the 84-day Skylab 4 mission, overtasking and ennui united to provoke a crew ‘rebellion’: for 24-hours no work was done, a sedition that resulted in none of the crew (Pogue, Carr and Gibson) ever flying again. During Salyut and Mir missions, arguments with ground controllers and irritability often surfaced in the middle mission. In addition, the long days and perceived lack of understanding of ground controllers frequently has led to an ‘us versus them’ attitude, with cosmonauts feeling increasingly isolated from and persecuted by ground controllers. Asthenia aside, spaceflight carries its own irritants, made worse by long duration. Simple head colds, non-draining and hence progressive in space, made the Apollo 7 crew (Schirra, Cunningham and Eisele) grumpy and argumentative; NASA removed them from active flying on return to Earth. Close quarters, recycled air and ‘defecation bags’ leave the Shuttle Orbiter smelling like a gym locker on return. Sweat from compulsory 2-hour daily exercise sessions floats off, hitting crew and equipment alike. Backaches and headaches abound in space (possibly from fetal posturing and fluid redistribution, respectively). Astronauts are not immune to the effects of irritants. I’m told one French astronaut even tried to make an unauthorized exit from the Orbiter in-flight, sans spacesuit, but have been unable to get details. Since predicting who will be affected by psychological stresses is half the battle, Russian scientists will commonly pack a prospective team of cosmonauts into a small car for an extended mid-winter trip around Russia, modeling the cramped quarters and isolation of spaceflight. With their decades of experience, Russian space docs also lead the field in recognizing psychological asthenia and stresses. During Norm Thagard’s stay on Mir, Russian Flight Surgeons identified the danger of too little work (most of the American experiments were ruined early on) before the Americans, and suggested ways of integrating Dr. Thagard into the daily routine. The Russian psychologists felt Jerry Linenger was not suited for long-duration spaceflight, and it was they who first recognized his lack of communication as a sign of withdrawal. Like the American astronauts, Russian cosmonauts have weekly private conference with their families, and weekly Medical conferences with their Flight Surgeons. In addition, cosmonauts and astronauts alike have an allowance by weight of personal effects to bring with them; books, tapes and videos are very popular (movie night is a popular pastime on Mir). Both Mir and the Shuttle Orbiter carry ham radios, for quick informal conversations with ham operators. Exercise is a popular stress-reliever, and astronauts and cosmonauts alike often get irritable if overtasking deprives them of their daily run. And in a liberty that American controllers look at askance, cosmonauts are allowed to bring small amounts of vodka aboard. Clearly, despite the paucity of media coverage and hard scientific data, psychological countermeasures play a considerable role in maintaining crew health, and can be expected to gain prominence as stays on ISS lengthen and piloted Mars missions draw closer.
Countermeasures vs. Re-Adaptation: Changing the Paradigm The overriding principle of Space Medicine, from the first speculations to the present day, has been to fight the body’s changes in microgravity: extended exercise to counter the muscle atrophy, drugs to maintain bone minerals, constrictive bands and negative pressure to prevent fluid redistribution. To date, our successes have been imperfect at best, counterproductive at the worst, and always awkward, bulky or uncomfortable. There is considerable evidence that most, if not ALL, of the body’s changes in microgravity have been physiological: measured responses, appropriate for maintaining the delicate equilibrium of the human body. Fluid volume redistributes and falls to a level appropriate for the new environment, then stays there; red cell count falls to a level consistent with a normal concentration, and does not fall further. The brain quickly learns to re-interpret the vestibular inputs correctly, and does not second-guess itself. Bones lose unneeded calcium and muscles shed unneeded mass, then remain unchanging at the new equilibrium. In short, the body adapts to its new environment, and maintains that adaptation as long as is appropriate. Time and again we have learned that, when we think we know what’s right for our bodies, we are either mistaken or find ourselves in agreement with the body’s natural responses. Consequently, there are those ‘space doctors’ who argue that any attempt to override the body’s natural adaptations with drugs and hardware is senseless and doomed to failure. Instead, they reason, we should focus our efforts on facilitating the body’s transition from one environment to another; minimizing discomfort and incapacitation, but not seeking to prevent its innate acclimatizations. While some difficulties arise from this philosophy (for example, the body’s unaided adaptations occur too slowly to prevent incapacitation immediately following orbital insertion and reentry), it seems to result in fewer conflicts than the ‘countermeasure’ paradigm. Instead of hours of strenuous exercise daily to maintain an ‘unnatural’ (artificial and contrived) muscle mass, moderate exercise (consistent with physical and psychological health) only would be required, and rebuilding of lost muscle mass undertaken only in the period preceding return to a higher gravity (e.g. from orbit to Mars or Earth). Instead of artificially maintaining a higher-than-needed fluid volume with constrictive bands, lower-body negative-pressure and fluid loading, a diuresis consistent with the lower pressure needs in microgravity would be allowed to proceed, and volume augmented only in the readaptation period before returning to a higher gravity field. In terms of extended spaceflight (e.g. a piloted Mars mission), this would entail a ‘pre-adaptation’ period, a time before entry into the new environment, during which measures to enhance the body’s acclimatizations to the new conditions would be instituted. It is likely that the duration of this pre-adaptation period would be proportionate to the magnitude of the upcoming change: the greater the change, the longer the period of acclimatization, to avoid overstressing the body. Thus, on completing the outgoing leg of a Mars mission, the anticipated pre-adaptation period for transition from zero-G to Mars’ 0.4 G would be shorter than that required for the return journey, a transition from zero-G to a full 1.0 Gs. If time-to-adaptation is linear, the pre-adaptation period necessary in Earth-orbit would be more than twice as long as that in Mars-orbit. As previously noted, countermeasures to adaptations to microgravity tend to be bulky, awkward and time-consuming; examples are the treadmill with heavy Vibration Isolating Mechanism to avoid hull stresses, the large and immobile cylinder for lower-body negative-pressure, high impact exercises (to combat loss of calcium) which require heavy hull materials and use of potentially dangerous drugs far from definitive medical care. Each of these demonstrates elements inappropriate for a light, fast and economical mission to Mars. If such countermeasures could be implemented in Low Earth Orbit (LEO), considerable weight, time and money could be saved, while increasing safety. Fortuitously, a vehicle for such pre-adaptation in LEO is already under construction: the International Space Station, or ISS. Before returning to Earth-normal gravity following extended exposure to microgravity, astronauts adapted to low gravity could live aboard the ISS and submit to countermeasures, necessary to readapt to full gravity but inappropriate to implement throughout an extended mission. Heavy and awkward hardware would be lifted only to LEO (rather than being sent to Mars), exercise periods during the mission could be geared towards relaxation and psychological comfort, and potentially dangerous physiological alterations (by drugs, body gear and strenuous exercise) would occur in the relative safety of Earth Orbit, where emergency medical evacuation is a possibility. Safety and comfort in deep space, on Earth and on Mars may be less a matter of changing our bodies than of altering our thinking. Pre-adaptation, rather than countermeasures, may be the way to ease our bodies into, and back out of, Space.
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