Test of Midodrine as a Countermeasure Against Post-flight Orthostatic Hypotension - Long (Midodrine-Long) - 01.09.14
Science Objectives for Everyone Test of Midodrine as a Countermeasure Against Post-Flight Orthostatic Hypotension - Long (Midodrine-Long) is a test of the ability of the drug midodrine to reduce the incidence or severity of orthostatic hypotension. If successful, it will be employed as a countermeasure to the dizziness caused by the blood-pressure decrease that many astronauts experience upon returning to the Earth's gravity.
Science Results for Everyone
Returning to Earth from space often causes a decrease in blood pressure, called orthostatic hypotension, this makes some crew members experience dizziness or fainting when standing shortly after returning to Earth. Orthostatic hypotension also affects people on Earth, and the drug Midodrine, which constricts blood vessels, has been shown to reduce its incidence or severity. This investigation tested its effectiveness on shuttle and ISS crew members coming back earth's gravity.
Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration:
October 2007 - October 2008
Previous ISS Missions
A precursor Supplemental Medical Objective (SMO) for Midodrine has been studied on STS-108, STS-110, STS-111, STS-112, STS-113 and ISS Expedition 5.
- Test of Midodrine as a Countermeasure Against Post-Flight Orthostatic Hypotension - Long (Midodrine-Long) is designed to evaluate the effectiveness of the drug midodrine at preventing low blood pressure (hypotension) that some astronauts experience upon returning to Earth.
- An in-flight ECG must be performed on subjects approximately 96 hours prior to TIG.
- Subjects ingest a dose of midodrine between Time of Ignition (TIG) and landing. Immediately after exiting the vehicle an operational tilt test will be performed.
Many astronauts experience postflight orthostatic hypotension, a condition where the blood pressure drops when an individual stands up, resulting in presyncope (lightheadedness) or syncope (fainting). Approximately 20-30 percent of crews on short-duration (less than 20 days) missions and 83 percent of crews on long-duration missions experience some degree of orthostatic intolerance after return to Earth. To date, the countermeasures tested, such as fluid loading, the use of lower body negative pressure (LBNP), and Fluronef, have not successfully eliminated postflight orthostatic hypotension.
On Earth, the drug midodrine has been used extensively to treat low blood pressure. . Midodrine acts as a vasopressor (raise blood pressure) by causing constriction (tightening) of the blood vessels which leads to an increase in blood pressure. Test of Midodrine as a Countermeasure Against Post-flight Orthostatic Hypotension - Short Duration Biological Investigation (Midodrine-SDBI) studies the effectiveness of midodrine for the treatment of postflight orthostatic hypotension.
Orthostatic hypotension (low blood pressure while standing) is a significant problem to astronauts returning from even short-term space flight, and the symptoms are more prevalent with longer-term flights. Often when returning home, an astronaut's body is unable to maintain blood pressure above the heart, which leads to decreased blood flow in the brain, resulting in lightheadedness and even fainting. Currently used countermeasures to the problem, such as increasing blood volume with saline, have not proven completely effective. If effective, postflight midodrine administration may provide a relatively simple method for preventing a significant obstacle to long-term space flight, especially exploratory trips to the Moon and Mars. Astronauts in this study, aside from being test subjects, are also control subjects for studies on Earth, as orthostatic hypotension in astronauts is temporary and they are otherwise healthy.
In addition to benefits for astronauts, millions of people on Earth suffer from orthostatic hypotension and may benefit from information gained from this experiment.
Crewmembers will ingest 10 milligrams of midodrine between Time of Ignition (TIG) and landing.
Approximately 90-days before flight, the participants will undergo a drug tolerance test for midodrine and will participate in a drug familiarization session. An operational tilt test will be conducted 10-days prior to launch, and the participants will complete a brief questionnaire before they leave the testing room.
Midodrine has been shown to successfully reduce orthostatic hypotension in patients on Earth, as orthostatic hypotension affects people other than astronauts. To date, this investigation has been performed on some space shuttle crewmembers and on an Expedition 5 crewmember. Further Expeditions will involve testing on more subjects before conclusive results can be determined.
Ground Based Results Publications
Ramsdell CD, Mullen TJ, Sundby GH, Rostoft S, Sheynberg N, Aljuri N, Maa M, Mukkamala R, Sherman D, Toska K, Yelle J, Bloomfield D, Williams GH, Cohen RJ. Midodrine prevents orthostatic intolerance associated with simulated spaceflight. Journal of Applied Physiology. 2001; 90(6): 2245-2248.
Tuday EC, Meck JV, Nyhan D, Shoukas AA, Berkowitz DE. Microgavity induced changes in aortic stiffness and its role in orthostatic intolerance. Journal of Applied Physiology. 2007; 102(3): 853-8.
Meck JV, Reyes CJ, Perez SA, Goldberger AL, Ziegler MG. Marked exacerbation of orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts. Psychosomatic Medicine. 2001; 63(6): 865-873.
Tuday EC, Meck JV, Nyhan D, Shoukas AA, Berkowitz DE. Microgravity induced changes in aortic stiffness and its role in orthostatic intolerance. Journal of Applied Physiology. 2007; 102(3): 853-8.
Shi S, Garcia KM, Meck JV. Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight. Journal of Cardiovascular Pharmacology. 2003; 41(1): 31-39.
Waters WW, Ziegler MG, Meck JV. Post spaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance. Journal of Applied Physiology. 2002; 92(2): 586-594.
Blood pressure gradient in someone with orthostatic hypotension: In a prone position, blood is evenly distributed throughout the body. When the individual stands (a position called orthostasis), however, their blood pressure is too low to pump sufficient amounts of blood above the level of the heart. Blood collects in the lower part of the body, temporarily depriving the brain, causing lightheadedness and possibly fainting. Astronauts may experience orthostatic hypotension for several days after landing. Image courtsey of NASA, Johnson Space Center.
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NASA Image: JSC2004E44665 - Astronaut Leroy Chiao (left), Expedition 10 commander and NASA International Space Station (ISS) science officer, and Russian Federal Space Agency cosmonaut Yuri Shargin (right) undergo physical testing on a mechanized tilt table at crew quarters in Baikonur, Kazakhstan, October 8, 2004, in preparation for launch to ISS. The tilt table is used to condition the crewmembers' cardiovascular system against the effects of weightlessness once on orbit. A similar tilt table will be used for the tilt tests in the Midodrine investigation.
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NASA Image: JSC2005E15226 - View of European Space Agency (ESA) astronaut Roberto Vittori and cosmonaut Sergei K. Krikalev during tilt table tests on April 11, 2005 in Baikonur, Kazakhstan.
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NASA Image: JSC2005E15228 - View of astronaut John L. Phillips during a tilt table test on April 11, 2005, in Baikonur, Kazakhstan.
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