Standing up to Gravity: Drug Shows Promise asTreatment for Orthostatic Intolerance in Astronauts

NASA has long sought a safe and effective countermeasure for orthostatic intolerance—the dizzy spells and feelings of faintness that often affect returning astronauts, a

consequence of their bodies’ adaptation to the microgravity of space. Studies by NASA-supported researchers suggest that a drug used to treat these symptoms in sick people on

Earth may help astronauts, too.

Space Life Sciences Research Highlights

On their return to Earth after a space mission,many astronauts feel dizzy and lightheaded—a condition known as orthostatic hypo-

tension or orthostatic intolerance. The problem ismore severe after long-duration space missions. Inan emergency, orthostatic intolerance could hinderan astronaut’s ability to exit a landed spacecraftwithout assistance.

Recent findings by NASA-supported researcherssuggest that a drug approved by the U.S. Food andDrug Administration (FDA) to treat orthostaticintolerance associated with disease may also allevi-ate the problem in astronauts returning to Earthfrom space.

Counteracting Gravity

When a person stands upright on Earth, the force ofgravity pulls his or her blood and other body fluidstoward the feet. However, the cardiovascularsystem has evolved an extensive set of mechanismsto counteract gravity.

“When you go from a lying to a standing position,your heart starts to pump faster to increase bloodflow,” explains Richard J. Cohen, Ph.D., of theMassachusetts Institute of Technology, who leadsthe cardiovascular research team at the NationalSpace Biomedical Research Institute. “The largeveins in your legs constrict, forcing more bloodback toward the heart, and your small arteries alsoconstrict. In healthy people, a whole network ofreflexes help to maintain appropriate blood pres-sure so we don’t feel dizzy when we stand up.”

Standing up too quickly can cause brief periods ofdizziness even in healthy individuals, but in mostcases the condition is transient and requires notreatment. However, some people with conditionssuch as diabetes or Parkinson’s disease sufferorthostatic intolerance as a result of nerve damagethat impairs their cardiovascular reflexes.

When astronauts go into space, the absence of gravitymeans their cardiovascular reflexes are no longer beingused. Their blood volume declines slightly and bloodand other fluids shift toward the head.

“The cardiovascular system adapts remarkably well tomicrogravity,” says Cohen. “However, when youreturn to Earth, your blood volume is somewhat lower,your cardiovascular reflexes have diminished, yourveins and arteries constrict less than they otherwisewould, and your heart’s pumping ability is reduced.”

As a result, insufficient blood flows to the brain,causing dizziness, lightheadedness, and sometimesfainting. These symptoms diminish within a few daysas the body re-adapts to gravity and those cardiovas-cular reflexes kick back in.

Tilt testing in the NASA JSC CardiovascularLaboratory to study the effects of orthostatictolerance preflight and postflight. Recordingsobtained include ECG, automatic blood pres-sure, beat-to-beat finger pressure, echocardio-graphic measurements, and respiratory tracing.Left to right: Janice Meck, Donna South, andDominick D’Aunno.

October 2003For additional information, contact: Office of Biological and Physical Research, National Aeronautics and Space Administration http://spaceresearch.nasa.gov

Drug Stimulates Blood Vessel Constriction

Janice Meck, Ph.D., director of the cardiovascularlaboratory at the NASA Johnson Space Center in Hous-ton, wondered whether midodrine—the first FDA-approved drug for treating orthostatic intolerance—might also relieve the condition in astronauts returningfrom space. Midodrine acts on receptors in the nervoussystem that stimulate the blood vessels to constrict.

Meck suggested to Cohen that, as a first step in testingthis hypothesis, his team study midodrine’s effect inhealthy male volunteers taking part in a bedrest study.Prolonged bedrest produces many of the same effectson the human body as exposure to microgravity does,including muscle deconditioning and orthostaticintolerance. For this reason, bedrest studies are anaccepted way of modeling the effects of microgravityon the ground.

Fifteen subjects spent between nine and 16 days lyingprone in bed with their heads tilted slightly downward.On the last day, they were randomly assigned to takeeither a low dose of midodrine or a placebo. The studywas double-blinded, meaning neither the researchersnor the subjects knew who received the drug and whoreceived the placebo.

Midodrine is a short-acting drug that reaches its peakeffectiveness about one hour after it is taken. An hourafter taking either the drug or the placebo, the subjectsunderwent a test of orthostatic tolerance known as a tilt-stand test. They lay flat on a table, one end of which wasslowly raised until they were standing upright. Theirblood pressure was monitored continuously. The testwas halted immediately if a subject’s blood pressuredropped suddenly or if a subject showed signs ofdizziness or lightheadedness.

“We found that about 75 percent of subjects in theplacebo group could not complete the tilt-stand test,”says Cohen. “Among the subjects who receivedmidodrine, only 29 percent were unable to tolerate thetest. These results were achieved using a very smalldose of the drug.”

Encouraging Results in Astronauts

Midodrine has also shown encouraging results intesting on seven returning shuttle astronauts. All sevenhad flown in space before; two had suffered orthostaticintolerance on returning from their previous mission.All seven took midodrine immediately after landing. Anhour later, they underwent the same tilt-stand test givento the subjects in the bedrest study.

“In both astronauts who had a history of orthostaticintolerance, midodrine corrected the problem,” saysMeck, who was the principal investigator for thisstudy. “The drug caused no significant adverseeffects in the five astronauts who did not have ahistory of orthostatic intolerance.”

Several characteristics of midodrine make it a promis-ing candidate for treatment of orthostatic intolerancein returning astronauts, says Meck. Unlike someother drugs that have been considered for this pur-pose, midodrine can be taken by mouth. It actsquickly, so astronauts can take it on landing orshortly before. Its effects wear off in a few hours andit has minimal side effects.

Meck cautions, however, that testing in a largernumber of subjects is needed before midodrine can berecommended for routine use in returning astronauts.

References1. Ramsdell CD; Mullen TJ; Sundby GH; Rostoft S;

Sheynberg N; Aljuri N; Maa M; Mukkamala R;Sherman D; Toska K; Yelle J; Bloomfield D; WilliamsGH; Cohen RJ. Midodrine prevents orthostatic intoler-ance associated with simulated spaceflight. Journal ofApplied Physiology 90(6):2245-8, 2001.

2. Ziegler MG; Meck JV. Physical and psychologicalchallenges of space travel: an overview. PsychosomaticMedicine 63(6):859-61, 2001.

3. Meck JV; Reyes CJ; Perez SA; Goldberger AL; ZieglerMG. Marked exacerbation of orthostatic intoleranceafter long- vs. short-duration spaceflight in veteranastronauts. Psychosomatic Medicine 63(6):865-73, 2001.

Tilt testing with ultrasound being performedin the JSC Cardiovascular Laboratory. Leftto right: Donna South, David Martin, andYuho Hayashi.