Phase I, Visit one Alpha (1A);
OIG (Orthostatic Intolerance Garment) Measurement:
Participants will lie supine while torso and anthropometric measurements are acquired.
The investigators will utilize the same procedures developed and adopted by the Orion
Program to obtain foot, leg, and torso circumference measurements at pre-determined
intervals. This detailed measurement procedure has shown to be effective at providing
precise compression levels at pre-determined anatomical locations. The target levels of
compression will be verified by the manufacturer, using a Hosiery and Allied Trades
Research Association (HATRA) test instrument that is identified in the British Standard
for testing compression in elastic stockings.
Tilt Familiarization:
Participants will be instructed to lie supine without moving throughout the
Familiarization tilt test. After instrumentation with brachial blood pressure, continuous
blood pressure monitoring, and electrocardiogram (ECG) for heart rate, baseline measures
will be obtained for at least 2 minutes while the test is explained. Participants will be
tilted to 80˚ head-up and instructed to remain still and quiet. After allowing the
participant to become familiar with the tilt procedure and the feeling of being upright,
the bed will be lowered back to horizontal (flat) and a timer started for a 20-minute
supine rest period.
Plasma and Blood Volume Measurement:
An intravenous (IV) catheter will be inserted into a vein in the participant's arm or
hand using standard techniques. All blood samples will be obtained using the IV catheter
in the participant's arm, unless it becomes clogged, and another IV catheter cannot be
placed in another arm or hand vein. In this situation, blood could be drawn from the
participant's arm or hand vein using a butterfly needle.
Participants will be supine for 20 minutes before this test begins. A clip will be placed
on the participant's nose so that they are breathing only through their mouth.
Participants will breathe through a mouthpiece connected to a rebreathing circuit
containing 100% oxygen, which is scrubbed by soda lime to remove carbon dioxide. After ~5
minutes, a ~10 mL blood sample will be collected using the IV catheter. Thereafter, a
small amount of carbon monoxide will be added into the breathing circuit, and the
participant will breathe this mixture of carbon monoxide and oxygen for ~10 min. Then, a
second ~10 mL blood sample will be obtained. Analysis of the blood samples (i.e.,
hematocrit, hemoglobin, and carboxyhemoglobin) will be used to calculate red blood cell
mass, plasma volume, and total blood volume.
Normovolemic Tilt Test at one unit of gravity (1G):
This test will be similar to the Tilt Familiarization session, but baseline data will be
collected for ~5 minutes while supine. After tilting up, participants will remain quiet,
relaxed, and not move for up to 20 minutes or until presyncope. Brachial blood pressure
will be measured, and ultrasound images obtained to quantify stroke volume approximately
every minute. Blood pressure and ECG will be continuously monitored before, during, and
after the tilt. A tilt test will be terminated if any of the following test termination
criteria are met: sudden drop in heart rate (>15 bpm), systolic blood pressure (>25 mmHg)
or diastolic blood pressure (>15 mmHg); significant cardiac arrhythmias such as an
ectopic rhythm >4 beats; absolute systolic blood pressure <70 mmHg; symptoms such as
nausea, clammy skin, profuse sweating, pallor, light-headedness, dizziness, or tingling;
or participant request. In the event a tilt test is terminated prior to 20 minutes, the
participant will be brought to a head-down tilt position until recovered.
Visit one Bravo (1B);
Plasma Volume + Furosemide Infusion:
Plasma volume will be measured as described in Phase 1A. After the plasma volume test is
complete, a 20 mg of Furosemide will be administered intravenously. This dose has been
demonstrated to produce plasma volume losses similar to spaceflight and bedrest. An oral
potassium supplement of 20 mEq (Milliequivalent) will be given as a prophylactic prior to
the furosemide infusion.
Induction of Hypovolemia:
Following Furosemide infusion, participants will remain in the CVL (Cardiovascular and
Vision Laboratory) and be observed while remaining seated (except for bathroom trips) for
2 hours. During this time urine volume and periodic blood pressure will be obtained.
Participants will self-collect urine using urine collection bottles and provide to the
test operator to document the time of urine collection and volume produced. Participants
will be given a standardized volume of water at intervals throughout the study day.
Participants will be provided snacks as needed throughout the duration of their stay in
the laboratory.
Hypovolemic Tilt Tests (1-G, 0.75-G, 0.50-G):
Following the 2-hour period for diuresis to develop, participants will undergo 3 tilt
tests (80°, 50°, and 30° head-up tilt) for up to 20 minutes each to simulate 1-G, 0.75-G,
and 0.50-G exposures. The tilt tests will occur in a random order and participants will
remain supine for 20 minutes to fully recover between tests. The timing, monitoring, and
test termination criteria will be identical to that described in Normovolemic Tilt Test
(1G) above. Immediately prior to each tilt test, a blood sample (5 mL) will be drawn
using the IV catheter and analyzed for hematocrit and hemoglobin concentration, which
will then be used to calculate the change in plasma volume since the baseline test.
Alternatively, if the IV becomes clogged and another IV cannot be placed, these blood
samples could be drawn from an arm or hand vein using a butterfly needle (5 mL) or by
pricking the finger (80 μL).
Phase II, Visit two Alpha (2A);
OIG Fit Check:
Participants will don their custom OIG garments to ensure there were no errors in garment
development.
Visit two Bravo (2B):
Plasma Volume + Furosemide Infusion Participants will complete the same testing protocol
as occurred in Phase 1B.
Induction of Hypovolemia:
Participants will complete the same testing protocol as occurred in Phase 1B.
Hypovolemic Tilt Tests (1-G, 0.75-G, 0.50-G) + OIG:
Following the 2-hour period for diuresis to develop, participants will don their
custom-made OIG and assume the supine posture for ~20 minutes prior to starting the first
tilt test. The order of the 3 tilt tests (80°, 50°, and 30° head-up tilt) will be the
same order as occurred in Phase 1B, Hypovolemic Tilt Tests (1-g, 0.75-G, 0.50-G).
Visits 2A and 2B can be combined.