Studies performed at the JSC Cardiovascular Laboratory reveal the disruptive adaptations of the heart and blood vessels to the upheavals caused by spaceflight and try to identify potential countermeasures to help protect the astronauts.

One of the first adaptations of the body to spaceflight is the adjustment of the cardiovascular system. Janice Meck, director of the Cardiovascular Laboratory at Johnson Space Center in Houston, Texas, has been studying the body's cardiovascular responses to spaceflight for many years. "Our mission is to document the [detrimental] cardiovascular changes that occur as a result of spaceflight, determine the mechanism of those changes, and develop countermeasures to prevent those changes," Meck explains.

Meck and her colleagues have concentrated on one primary problem that has recurred in many astronauts, that of orthostatic hypotension, or low blood pressure upon standing or sitting. For the first few days after returning from a short-duration spaceflight, approximately 20 percent of astronauts find it difficult to maintain a proper blood pressure when they move from a lying down position to either sitting or standing. Their symptoms range in severity from simple lightheadedness, or presyncope, to actual fainting, or syncope. This problem has several mechanisms, all related to the body's responses and adaptations to microgravity. Orthostatic intolerance is caused by three factors that are related to each other: 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. (For information on a study using rats to understand the mech-anisms of these cardiovascular adaptations, see "The People of STS-107," p. 6. (/general_info/sts107people.html) )

John Glenn, World's First 77-Year-Old Astronaut When John Glenn returned to space on shuttle mission STS-95 in 1998, Janice Meck, of the Cardiovascular Laboratory at Johnson Space Center, studied his cardiovascular response to spaceflight closely. Above: When John Glenn flew as a payload specialist for the STS-95 mission aboard Space Shuttle Discovery, he became the oldest astronaut ever to go into space. His mission enabled NASA researchers to study the effects of aging on the cardiovascular system's ability to adapt to spaceflight. Surprisingly, Meck discovered that the differences that age had made in his body better equipped Glenn to handle the cardiovascular adaptations to a microgravity environment. When Glenn returned from orbit, far from feeling faint or suffering from cardiovascular stress, he was calm and downright chipper. Meck remembers, "He was standing there laughing at me when I was trying to tell him to be quiet during his tilt test. He was not in any stress at all."An older person has a different strategy than a young person in maintain-ing blood pressure," explains Meck. Glenn had a high release of norepinephrine, which helps maintain pressure, both before and after spaceflight. This response is typical of the elderly and for Glenn, this resulted in a normal level of vascular resistance. Glenn also had a higher cardiac output than the other male astronauts, possibly due to a greater venous return. This higher output, coupled with a normal vascular resistance, enabled Glenn to maintain an adequate blood pressure on landing day. These research results were published in Rossum, A., Ziegler, M., & Meck, J. (2001). Effect of spaceflight on cardio-vascular responses to upright posture in a 77-year-old astronaut. The American Journal of Cardiology, 88, 1335-7 (Abstract (http://www.elsevier.com/locate/inca/525048) ).

Changes in Blood Distribution

On Earth, because of the downward pull of gravity, the body easily supplies blood to the lower limbs. The challenge is in supplying it to the upper extremities. To do this, the upper body is equipped with receptors that monitor and help maintain blood flow and pressure. In microgravity, blood volume shifts toward the head, resulting in more blood than is usual in the upper portion of the body. This increase triggers the receptors, which then cause the body to reduce the volume of the blood.

Once the blood volume is reduced, explains Meck, "then those receptors become happy again and there is a normal blood volume in the chest. However, there is less blood in the legs. Now that's just fine as long as you're up in space." But when astronauts return to Earth, the bulk of the blood goes back down to the legs, and because the total amount of blood has decreased, there isn't enough to fill up the whole system of blood vessels. This contributes to the occurrence of orthostatic hypotension.

Neurotransmitters "Forget"

Another contributor to this problem is the autonomic nervous system, which helps control blood pressure, among other things. Normally, this system is responsible for making minute and immediate adjustments to the cardiovascular system in order to maintain the blood flow and pressure. The system does this by releasing a neurotransmitter called norepinephrine that causes the blood vessels to constrict to keep the pressure at the appropriate level to supply an adequate amount of blood to the body's organs. "When you go up into space," explains Meck, "those mechanisms aren't really necessary, so besides the fluid shift that makes you lose the plasma volume, it seems that perhaps those mechanisms 'forget' [their function]." The degree of this "forgetfulness" appears to be directly proportional to the duration of the spaceflight.

Orthostatic hypotension is also caused by the blood vessels. "The vessels themselves can try to control the amount of blood getting to the organ they're serving," says Meck. She gives the example of a blood pressure cuff inflated to the point where there is no blood flow through the vessels of the arm. "The arm's vessels dilate to try to get flow going. If the cuff is suddenly released, the dilated vessels allow the blood to rush back into the arm. This increases shear stress, which actually stimulates the lining of the blood vessels to release additional vasodilators, ensuring that the arm will get better flow." This mechanism is called reactive hyperemia. Similarly, when an astronaut returns to Earth and blood rushes to his or her legs, the vessels might respond not by constricting, to force the blood back up, but by dilating further, which permits more flow downward and less pressure, resulting in less blood in the astronaut's upper body and head.

Changes in the Heart

The heart itself is also a factor in orthostatic hypotension. Some data from the Neurolab mission, which flew in 1998 with a payload exclusively geared toward life sciences research, suggest that in micro-gravity "the heart might be a little bit stiffer and not be able to maintain its output as well," explains Meck. Short-duration flights, such as shuttle missions, do not appear to have much of a detrimental effect on the heart. The problem, as is only now becoming apparent, is with long-duration flights. "We're definitely seeing changes in the way the heart works [during long-duration flights]. . . . We've documented ventricular dysrhythmias [irregular heartbeats] after about a month in flight," explains Meck.

During their research into orthostatic hypotension, Meck and her colleagues have discovered that there are some identifying clues that can lead researchers to predict which astronauts will become presyncopal or syncopal after spaceflight. Astronauts who have lower vascular resistance and arterial pressure before flight do not have a sufficient resistance after spaceflight to maintain pressure and thus are presyncopal or syncopal on landing day.

Women More Susceptible

Another discovery made in recent studies is that there is a significant difference between women and men in their bodies' abilities to maintain blood pressure after spaceflight. Women generally have a higher heart rate and a lower vascular resistance than men. Thus, when female astronauts return from space, their vascular resistance, already low, is insufficient to combat the lower blood volume. In a recent postflight analysis after a short-duration spaceflight, 100 percent of female astronauts became syncopal versus only 20 percent of male astronauts.

Although much has been learned about the mechanisms involved, the problem of orthostatic instability has proved a hard nut to crack. One possible countermeasure is the drug midodrine. "Midodrine is a vasoconstrictor," says Meck, who is studying the drug's effects. "It's a really good candidate because it doesn't cross the blood/brain barrier. Most things that can act to constrict and raise blood pressure also affect the brain." Other advantages of midodrine are that it has its peak effect in an hour, reducing the risk of repeat doses due to delayed landings, and has a half-life of four hours, sufficient to help the astronauts during most of the critical landing day, when the effects of orthostatic instability are the greatest.

Multiple Solutions

The solution to orthostatic intolerance in astronauts will likely be more complex than a single drug prescription. "The cardiovascular problems associated with spaceflight are multifactorial. You might need four or five different countermeasures in some combination to solve the problem completely," says Meck.

Meck and her colleagues have many plans for future research investigating all the factors of orthostatic hypotension. Paramount is further exploration of the negative effects of long-term spaceflight on the heart itself and of why the autonomic nervous system seems to "forget" to maintain vascular resistance the longer an astronaut is in space.

Above: Scientists at Johnson Space Center's Cardiovascular Laboratory use a controlled tilt test to replicate the body's responses to a shift from reclining to sitting or standing. Here, Janice Meck (far left) and Donna South (center) demonstrate the procedure with the help of Dominick D'Aunno (right).

Meck's research is especially valuable now that NASA is poised on the edge of longer-duration spaceflights. For long flights, the percentage of astronauts who suffer from orthostatic hypotension rises from 20 to 80. Meck's research may also benefit the half a million people on Earth who suffer from orthostatic intolerance. Some have symptoms so severe that they are unable to lead normal lives. Meck's research with the astronauts is closely watched by doctors treating these ground-based patients.