Out of this world physiology

URBANA, ILLINOIS — In his five months on the space station Mir in 1997, Jerry Linenger endured a fire, a faulty oxygen generator, and a failed cooling system that leaked antifreeze fumes and temporarily converted the cabin climate to rain forest redux. But he still managed to monitor himself adequately enough to document a new risk of long-term manned space flight, a type of prolonged jetlag that could impair the performance of astronauts over long missions.The study, reported in November/December Psychosomatic Medicine, is one of a number of recent studies on manned space flight that have raised serious concerns about how long humans can stay healthy in space. They also shed new light on various aspects of human physiology — in both normal and diseased states.Diurnal rhythms in humans affect sleep-wake cycles, body temperature, alertness and the performance of a variety of tasks. These are controlled by external cues such as sunlight and darkness, the social rhythms of human society and by an endogenous circadian pacemaker (ECP). In space, however, these external cues are dramatically altered. For example, day and night cycled every two hours on Mir as the space station sped around the earth. To see if the ECP functioned normally over long space flights, Timothy Monk, Professor of Psychiatry at the University of Pittsburgh Medical Center, designed measurements of body temperature and alertness that Linenger carried out five times a day during three two-week periods at the beginning, middle, and end of the five-month mission. During those periods, Linenger also closely monitored when and how long he slept, how often he woke up in the middle of the night and the quality of his sleep.An earlier study had shown that the ECP of monkeys was disrupted in space, but previous work by Monk's team had shown no signs that human circadian rhythms decayed during a 17-day mission. In the current study, Linenger's circadian rhythms were maintained for three months in space, but then began to deteriorate, despite the astronaut's efforts to hold himself to a regular sleep schedule corresponding to the 24-hour day on earth. Linenger's body temperature, which oscillated over a range of about 0.4°C each day while his ECP was intact, changed less than half that amount late in the mission. And his assessment of his own alertness followed the same pattern: late in the mission, he didn't feel sleepy at bedtime and had to force himself to go to bed. "What we found was very interesting," Monk reported. Linenger's circadian rhythm "wasn't drifting out of phase; it was just losing its umph….One way to interpret [the results] was that the message was not getting through from the biological clock," he added.According to Monk the results need to be replicated in other astronauts, but if they are similar, astronauts will need to take measures — for example exposure to bright lights, or exercise — in order to counter these effects. These same tactics might also help ordinary earthbound men in their 70s and 80s, who suffer from insomnia and fragmented sleep in the night and early morning. "All of us developed on this planet with a 24-hour rotation. It permeates the whole essence of biology. When we move off the planet as explorers or colonists, we have to answer some profound questions about how our 24-hour biology is going to function in those situations," Monk continued.Without the constraints of the 24-hour day and gravity, human physiology undergoes other changes, some of them dramatic, said Michael Ziegler, Professor of Medicine at the University of California, San Diego. Studying the physiology of astronauts who are deprived of diurnal cues and gravity is similar to studying the physiology of a genetic knockout mouse with a defective gene. The results shed light on the normal function of what's missing.The "loss of gravity does a lot of things to a lot of systems that we ordinarily don't think about," Ziegler said. Digestion is altered, as is circulation and fluid distribution throughout the body. So are bones, which tend to dissolve over time as in osteoporosis, and the vestibular system, which normally helps maintain balance and gait, he said.For example, in another study in the current issue of Psychosomatic Medicine, Ziegler and Janice Meck, a physiologist at NASA's Johnson Space Center in Houston, examined a problem that sometimes occurs when astronauts return to earth: a temporary inability to stand up without fainting. On earth, gravity pulls blood down from the upper parts of the body. The blood flow is controlled by nerves that control circulation, by one-way valves in veins and by threading blood vessels through skeletal muscles, which contract to help deliver blood back up to the heart and head. "When [astronauts] come back to earth, a lot of that stuff goes haywire," Meck said.About 20% of astronauts have this problem, called orthostatic intolerance, after returning from short-duration flights lasting about two weeks, Meck said, although they generally recover in about three days if they consume a lot of salt and drink a lot of water. But in their current study, Meck's team showed that the cardiovascular effects may get worse with time: usually, only about 20% of male astronauts have problems standing up, but after stints in Mir lasting between four and six months, five of six astronauts were affected. One of these men had flown before and had no problems on that occasion, suggesting but not proving that "the effects of long duration space flight might be more severe," Meck said.What's more, if methods to combat the problem are found for astronauts, they could help treat patients with postural hypotension — a chronic and debilitating disorder with similar symptoms, Ziegler suggested.Another study on astronauts from the same team could shed light on what makes people susceptible to high blood pressure. In an effort to find out what makes astronauts susceptible to orthostatic intolerance, Meck, Ziegler and their colleagues examined astronauts before they went into space and found two distinct populations whose cardiovascular systems respond very differently to standing up. Harm et al. in November Journal of Applied Physiology showed that one group demonstrated a greater degree of smooth muscle constriction of their blood vessels and this group ends up with less orthostatic intolerance. This trait could offer a new way to spot a tendency to develop high blood pressure, she said.Other insights into normal circulation are coming from studies of astronauts. For example, it has been revealed that without gravity pulling blood downward, drugs in inhaled aerosols are poorly absorbed in the lung. This means that our pulmonary circulation has evolved to use gravity to direct blood to exactly where its needed to absorb oxygen, Ziegler concluded.Besides cardiovascular problems, groups working on space flight worry most about long-term bone loss, and research on astronauts could lead to new treatments for osteoporosis. "Bones dissolve in space, and they dissolve nonstop," he said.Evidence of this problem came from a study of a Russian cosmonaut whose bones were still dissolving after a year on Mir, and it could pose a real risk to Caucasian women on long space flights because this group is more susceptible to osteoporosis. The problem could lead to more fractures on returning to gravity, as well as higher risks of kidney stones, which contain crystallized calcium from dissolving bones. Testing different ways to prevent bone loss for astronauts, including drugs and exercise regimes, could identify ways to slow bone loss in people prone to osteoporosis.Studying the effects of space flight on astronauts and experimental animals, said Monk, "We can not only answer the practical question of whether we can travel to Mars. [Such studies also] "help us to understand the rhythmic path of our being, which is so inherently part of the biology of practically every living thing on Earth", concluded Monk.

Out of this world physiology

The way in which the human body responds to the rigours of space flight is providing insights into Earthly physiology.

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