To date, available countermeasures (LBNP, fluid loading, Florinef) have not eliminated postflight orthostatic hypotension. This study was designed to evaluate a new pharmacologic countermeasure for protection from postflight orthostatic hypotension. Investigators were studying the ability of the drug Midodrine to reduce the incidence and/or severity of orthostatic hypotension in astronauts returning to Earth. The subject pool included subjects who experience presyncope as well as those who do not. Midodrine is a selective alpha-1 adrenergic agonist that is used clinically to treat orthostatic hypotension. It is almost completely absorbed after oral administration and is hydrolyzed enzymatically to its active metabolite, desglymidodrine, which has a bioavailability of 93%. Midodrine acts by increasing vaso- and venoconstriction, thereby decreasing peripheral venous capacity and blood pooling, but does not pass the blood-brain barrier and therefore has no central stimulant effects. The effect of midodrine as an alpha-adrenergic agonist may be particularly protective of orthostatic tolerance in astronauts who become presyncopal on landing day due to inadequate release of norepinephrine.
Data sharing from the Medical Operation’s Tilt Test (MR001L) performed on L-10 days was required, along with a brief questionnaire to be completed by the crewmember before leaving the test room. For the Operational Tilt Test, subjects were instrumented with an electrocardiogram, a beat-to-beat finger blood pressure device, and an automatic blood pressure cuff. Echocardiographic measurements (measurements of blood vessels by non-invasive ultrasound) were made to determine aortic cross-sectional diameter and aortic flow while lying on a tilt table. Using a tilt table, the subject was brought upright and supported by the tilt table at 80? for 10 minutes while the measurements continued.
In flight: Crewmembers participated in their scheduled in-flight activities without restriction for the duration of their Shuttle mission. After the decision for deorbit burn was confirmed on the scheduled landing day, crewmembers donned the Advanced Crew Escape Suit (ACES) and ingested 10 mg of midodrine approximately one 1 hour before the scheduled landing time. The midodrine pill and a cue card with medication instructions had been stowed in the subjects’ ACES for their convenience. All crewmembers participated in the standard oral fluid-loading protocol and inflated their antigravity suits during reentry and landing.
Postflight: Shortly after return to Earth, an Operational Tilt Test (MR001L) was performed in the Crew Transport Vehicle (CTV) to determine the crewmember’s orthostatic tolerance. The subject was instrumented with an electrocardiogram, a beat-to-beat finger blood pressure device, and an automatic blood pressure cuff. ECG measurements were made to determine aortic cross-sectional diameter and aortic flow while lying on a tilt table. Following this, the subject was brought upright by the tilt table to approximately 80 degrees for 10 minutes while the measurements continued. The tilt test was used to assess the effects of prolonged weightlessness on orthostatic tolerance during upright posture, as measured by supine and standing heart rate, blood pressure, stroke volume, cardiac output and total peripheral resistance. After completion of the Tilt Test, blood pressure was monitored at regular intervals for an additional period of time. During this time the crewmember also completed a questionnaire.
It is critical that the postflight Operational Tilt Test was performed within 2.5 hours of pill ingestion. Arrangements were made to perform the postflight data collection on the CTV to accommodate this time interval.
Midodrine appears to prevent orthostatic intolerance in test subjects after bed rest and in astronauts after space flight when testing is conducted in a controlled laboratory setting within 2 to 4 hours after landing. It is unclear at this time whether similar effects can be expected during reentry and immediately after landing, particularly in warmer environments and/or when the crewmembers are still wearing the ACES. Accurate interpretation of the current data requires that similar data be collected in control subjects (without midodrine) on the CTV. However, concerns about drug interactions with commonly used anti-emetics and prolonged QTc intervals observed in astronauts returning from long-duration missions make the routine use of midodrine unlikely and reliance on lower-body compression garments preferable.