Orthostatic intolerance

Most astronauts do have the right stuff, at least until they come back down to Earth. Then, many get dizzy and lightheaded when they simply stand in one place for a while. This unsettling effect can last for days or weeks. "When astronauts come back to Earth, a lot of stuff goes haywire," says Janice V. Meek of the Life Sciences Research Laboratories at NASA's Johnson Space Center in Houston. What makes them dizzy is a temporary dysfunction of their circulatory system. Though probably no more than an inconvenience for astronauts, the phenomenon has led to a better understanding of a longer lasting condition that, for some people, makes just standing up a challenge all the time. People with the condition, now usually called orthostatic intolerance, may experience accelerated heartbeat, faintness, nausea, or dizziness when they stand.

"I think that this disorder is tremendously complicated and probably underdiagnosed," says Julian Stewart of New York Medical College in Valhalla. Moreover, he says, orthostatic intolerance is often misdiagnosed as a heart problem, migraine, or psychiatric disorder.

The symptoms of orthostatic intolerance also overlap with those of chronic fatigue syndrome. Recently, Stewart showed that many teenagers diagnosed with chronic fatigue syndrome actually have a form of chronic orthostatic intolerance that's called postural tachycardia syndrome. It impairs blood flow and heart rate and sometimes causes a fall in blood pressure.

Though fainting is uncommon among them, these young people have some of the dizziness and nausea as well as fatigue, headache, pallor, and difficulty thinking. "My take is that young patients who fulfill the case definition for chronic fatigue syndrome probably have orthostatic intolerance," says Stewart. That's helpful to know because there are more effective treatments for orthostatic intolerance than for chronic fatigue, he says.

CIRCULATION 101 Here on Earth, gravity makes the task of getting blood to the brain literally an uphill battle. After all, physics dictates that the large volume of blood in the chest and heart stays where it is or runs down to the feet. Fighting gravity is even more challenging as a person stands up from a chair or bed. In that circumstance, to maintain adequate blood pressure and move blood toward the brain, the body instantly increases its heart rate and constricts major blood vessels. Even so, the brain may receive less oxygen than it normally does, and most people occasionally experience transient dizziness, faintness, or hazy vision if they stand up too quickly.

"A useful analogy might be to a fireman trying to get water to the roof of a house which is on fire," says Benjamin Levine, a physiologist with the University of Texas Southwestern Medical Center at Dallas. "To get the water higher, the fireman can either turn the pump up faster, similar to increasing the heart rate, or put his or her finger over the end of the hose to get more pressure, similar to constricting the blood vessels."

In fact, says Levine, measurements of vein size and capability to constrict blood vessels may predict which people are most likely to develop orthostatic intolerance after a space flight.

"Because gravity plays such a critical role in determining the pressure and distribution of blood flow within the circulation, the absence of gravity such as occurs in space flight affords a unique environment [in which] to examine these control systems," he says. The systems include nerves that govern heart rate and blood vessel constriction, one-way valves in veins, and skeletal muscles that help push along the blood in vessels threading through them.

Maintaining blood pressure while upright begins with the autonomic nervous system, which operates without a person's awareness. Signals come into this system from pressure sensors, called baroreceptors, located in crucial areas of the heart and the arteries feeding the brain. When the baroreceptors sense low blood pressure, they generate signals that cause nerves of the autonomic nervous system to speed up heart rate and constrict blood vessels. when blood pressure is high, another part of the autonomic nervous system kicks in to reduce blood flow by slowing the heart rate and relaxing the blood vessels.

Evolution has endowed people with a back-up system for regulating blood flow to the brain. Blood vessels in the brain can constrict or dilate to keep blood flow constant there, even when blood pressure changes in the rest of the body.

Signals can, and do, get crossed in such complicated systems. However, recent research on physiological responses to space flight, published in three papers in the January Journal of Physiology, indicates that all of these systems are working :normally in astronauts, says David Robertson of Vanderbilt University Medical Center in Nashville, lead author of one of the papers.

HIGH-FLYING PHYSIOLOGY "The great advantage [of studying astronauts] is that it gives us a chance to study someone before they have orthostatic intolerance, as they are getting it, when they have it, and after they've recovered," says Robertson. "It gives us a chance to follow physiology over time."

Which is exactly what he and his colleagues did in 1998. That year, during and after a 16-day space shuttle mission dubbed Neurolab, the scientists performed many tests on the mission's astronauts. The astronauts also performed some of these tests on themselves while in orbit.

One finding was that astronauts lose 10 to 20 percent of their blood volume during space flight. The most probable explanation, say the researchers, is that the fluid in the blood slips out of the circulatory system into tissues--causing puffiness and swelling but less blood volume--or that the excess fluid in the astronauts' upper body signals the kidneys to excrete fluid as urine. In either case, blood that normally would flow to and from the extremities lingers in the body's core.

Extended bed rest mimics the effects of low gravity and so is often used to explore the effects of space flight. Like astronauts, people on bed tend to increase urination to excrete the fluid that pools in their chests and abdomens.

Not all astronauts have the same degree of difficulty after they return to terra firma. The longer astronauts had remained in space, the more common it was for them to experience dizziness back on Earth, Michael Ziegler of the University of California, San Diego and his colleagues reported in the November/December 2001 Psychosomatic Medicine.

Some previous research had shown that the astronauts with the worst orthostatic intolerance after a space flight had the lowest blood concentrations of norepinephrine, a neurotransmitter released by the sympathetic nervous system to contract blood vessels and boost blood pressure.

Contrary to expectations, however, the Neurolab studies showed that the norepinephrine concentrations were actually higher than normal in all the astronauts' blood while they orbited. This, apparently, enables astronauts to maintain normal blood pressure despite the loss of blood volume.

Levine surmises that when some astronauts stand up on Earth after a mission, their higher-than-normal norepinephrine concentrations make it harder for them to further constrict their blood vessels and counteract gravity's pull. Thus, some of the wooziness that astronauts experience once they get back down is a natural reaction to physiologic changes that were helpful in space.

Norepinephrine is only a chapter of the story. The heart itself contributes to the problem even more, Levine, Robertson, and their colleagues conclude. The heart doesn't have to work as hard in space as it does on Earth. In space, it doesn't have to fight gravity. Also, because an astronaut loses blood volume, there is less blood for the heart to pump in each beat.

The heart responds to these reduced demands by temporarily shrinking. It also becomes stiffer because its chambers are stretched less with each beat and--like a rubber band--don't contract as strongly or as quickly as they would if stretched fully.

DOWN TO EARTH Recognition that an environmental change such as space flight or bed rest could trigger a full-blown medical syndrome in otherwise healthy people has prompted more physicians to recognize orthostatic intolerance in their patients, Levine notes.

Researchers agree that tests developed for the space missions, such as measuring beat-by-beat blood pressure, have simplified the diagnosis of orthostatic intolerance in patients. Even so, pinpointing causes of the condition and identifying appropriate treatments remain challenging. Many things can trigger the syndrome, including bed rest, dehydration, some drugs, genetic defects, abnormal nervous system regulation of blood pressure, and neurological conditions such as Parkinson's disease (SN: 5/11/02, p. 293). Several scientists have concluded that, like astronauts, many people with orthostatic intolerance have lower-than-normal blood volume.

A couple of years ago, Robertson and his colleagues identified a family with heritable orthostatic intolerance. The family members turned out to have a genetic mutation that prevents the body from breaking down norepinephrine after it's done its job. That creates a situation similar to that of astronauts who produce extra norepinephrine to compensate for their reduced blood volume in orbit.

Teasing out the underlying causes of orthostatic intolerance can help guide treatment, Levine says. Some therapies are simple. For example, many doctors recommend that people with orthostatic intolerance drink extra water and consume salt to increase their blood volume. They also tell their patients to wear elastic support hose and to move around before and after standing up. That motion can increase nerve activity and boost blood pressure in the legs, thereby prepping the body to pump blood upward.

A drug called midodrine, recently approved by the Food and Drug Administration for boosting low blood pressure by increasing sympathetic nerve activity, also seems to help people with orthostatic intolerance. Stewart is testing the drug in his group of teens with postural tachycardia syndrome. This year, NASA plans to see whether taking midodrine before their spacecraft lands can help astronauts reduce subsequent orthostatic intolerance.

Such a drug may not be necessary for space travelers, Levine says. He suggests, for example, that it may be enough for astronauts to exercise during space flight--to prevent the heart from shrinking--and to drink extra fluid just before returning to Earth. Preliminary studies of people on bed rest suggest that combining these two treatments is quite effective in preventing orthostatic intolerance, he says.

Finally, Levine recommends that some of his patients simply elevate their heads while they sleep. This has two benefits. First, people with orthostatic intolerance face less of an abrupt change in blood flow when they stand up from such a position. Second, he says, tilting the bed up this way keeps the body accustomed to working harder to pump blood to the head.

Levine concludes that people with orthostatic intolerance are, in effect, not as well adapted to gravity as they should be. So, whatever treatments for the disorder emerge, they should have applications both in and out of this world.

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