Test of Midodrine as a Countermeasure Against Post-flight Orthostatic Hypotension - Short Duration Biological Investigation (Midodrine-SDBI) - 01.09.14
Science Objectives for Everyone Test of Midodrine as a Countermeasure Against Post-Flight Orthostatic Hypotension - Short Duration Biological Investigation (Midodrine-SDBI) 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
A crew member who experienced post-flight orthostatic hypotension, or dizziness, took midrodine after a second flight and researchers compared heart rate, blood pressure, and cardiac volume between the two flights. The midodrine appeared to protect this previously susceptible crew member, suggesting a single dose shortly after landing could help prevent the problem. Researchers also tested the drug on five astronauts not previously affected by orthostatic hypotension and found it seemed to preserve normal upright blood flow, and was well-tolerated by test subjects. These results indicate that midodrine could be a possible medicine to help prevent the symptoms of post-flight orthostatic hypotension.
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:
September 2006 - April 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 - Short Duration Biological Investigation (Midodrine-SDBI) is designed to evaluate the effectiveness of the drug midodrine at preventing low blood pressure (hypotension) that some astronauts experience upon returning to Earth.
- 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% of crews on short-duration (less than 20 days) missions and 83% of crews on long-duration missions experience some degree of orthostatic intolerance after return to Earth. To date, the countermeasures tested--e.g., fluid loading, the use of lower body negative pressure (LBNP), and the medication 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.
Shuttle 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, was given to an astronaut subject after landing in a second flight, who experienced orthostatic hypotension after a previous flight, to determine if the drug is effective in alleviating these symptoms. Heart rate, blood pressure (BP), and cardiac volume were compared between the two flights. Data show midodrine prevented severe falls in stroke volume, cardiac output, systolic pressure, and severe increases in heart rate without increasing blood flow resistance, thus preventing orthostatic hypotension. The significance of this finding is that midodrine appeared to protect a previously susceptible astronaut from post space flight orthostatic hypotension. These results suggest that a single, 10-mg oral dose of midodrine shortly after landing may have the potential to protect astronauts from post space flight orthostatic hypotension (Platts et al. 2004). A follow on study using the same protocols with five astronauts who had not been susceptible to orthostatic hypotension following their previous space flights shows that there were no statistically significant differences between blood pressure or cardiac output. No subject experienced reduced BP or fainting symptoms during any test. Blood-flow responses were very similar between flights. Of note, however, is that mean post-flight upright heart rate was significantly higher than the preflight baseline for the control flight, but was not after midodrine treatment compared to respective preflight upright heart rates. Importantly, the drug did not result in significantly increased supine (lying down) or upright BP. Additionally, supine stroke volume tended to be higher after midodrine, compared with preflight. There were no striking differences of blood-flow indicators between the control and midodrine tilt responses, but the data suggest a modest beneficial effect. Although no subjects had low BP following their control flights, increases in heart rates during tilt test on landing day indicate that they were less tolerant of the procedure than before flight. They had a less pronounced increase in heart rate, and standing systolic BP tended to be higher after taking midodrine. Thus, there was a trend for midodrine to preserve normal upright blood flow and improve tolerance for the post flight tilt test. These results, combined with bed rest studies, suggest that midodrine may help prevent post-flight fainting and orthostatic hypotension symptoms, and the drug appeared to be well tolerated in these test subjects (Platts et al. 2006).
Platts SH, Ziegler MG, Waters WW, Meck JV.Midodrine Prescribed to Improve Recurrent Post-Spaceflight Orthostatic Hypotension. Aviation, Space, and Environmental Medicine. 2004; 75(6): 554-556.
Platts SH, Ziegler MG, Waters WW, Meck JV. Hemodynamic Effects of Midodrine After Spaceflight in Astronauts Without Orthostatic Hypotension. Aviation, Space, and Environmental Medicine. 2006; 77(4): 429-433. PMID: 16676655.
Waters WW, Ziegler MG, Meck JV. Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance. Journal of Applied Physiology. 2002 February; 92(2): 586-594. DOI: 10.1152/japplphysiol.00544.2001. PMID: 11796668.
Ground Based Results Publications
Martin DS, Meck JV. Presyncopal/Non-Presyncopal Outcomes of Post Spaceflight Stand Tests Are Consistent from Flight to Flight. Aviation, Space, and Environmental Medicine. 2004 January; 75(1): 65-67.
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.
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.
Arai T, Lee K, Stenger MB, Platts SH, Meck JV, Cohen RJ. Preliminary application of a novel algorithm to monitor changes in pre-flight total peripheral resistance for prediction of post-flight orthostatic intolerance in astronauts. Acta Astronautica. 2011 April; 68(7-8): 770-777. DOI: 10.1016/j.actaastro.2010.10.008.
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.
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. Microgavity induced changes in aortic stiffness and its role in orthostatic intolerance. Journal of Applied Physiology. 2007; 102(3): 853-8.
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.
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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