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.Principal Investigator(s)
Johnson Space Center, Human Research Program, Houston, TX, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Information PendingISS Expedition Duration:
October 2007 - October 2008Expeditions Assigned
16,17Previous 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.
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.Earth Applications
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.Operational Protocols
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.
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.
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.
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.
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.
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.