Physiological Parameters that predict Orthostatic Intolerance after Spaceflight

1. Principal Investigator: John M. Karemaker Co-Investigators: Janneke Gisolf Johannes J. van Lieshout Wim J. Stok J.Phillip Saul Academic Medical Center at the University of Amsterdam, dept. of Physiology, The Netherlands Sponsored by Space Research Organisation Netherlands (SRON) Physiological Parameters that predict Orthostatic Intolerance after Spaceflight

2. Background & scientific hypothesis Description of experiment and its objectives Description of equipment used, hazards and discomforts Summary Lesson outline / Contents

3. Postflight Orthostatic Intolerance (OI) [i.e. dizziness or even fainting when upright] may lead to immediate danger at critical moments during the return flight and landing. Need for reliable in-flight countermeasures. Project goal: to define a set of preflight tests that predicts who is more liable to develop postflight OI. Background

4. Postflight OI can be predicted by testing cardiovascular control quality, using non-invasive cardiovascular measurements. - ECG (mainly for heart rate measurement) - thoracic impedance; - finger blood pressure (Finapres); - TransCranial Doppler (TCD) blood flow velocity of the middle cerebral artery; Hypothesis

5. Finapres

6. Transcranial Doppler (TCD)

7. Fully instrumented subject (Co-I) on the tilt tablewith TCD, breathing detection and Finapres in place

8. Measure cardiovascular responses to dynamic challenges induced by: Tilt table; Paced breathing; Thigh-cuffs: inflated or deflated. Results preflight vs. duration of postflight standtest Objectives

9. Tilt table

11. Session Description Preflight (I) L-180 lab session in Amsterdam (3hrs) Cardiovascular reflex responses to challenges on tilt table: - fast tilt up: supine  upright; - paced breathing (from ~ 1 per 15s. to 1 per 3s. supine & upright); - thigh-cuffs (inflated or deflated). - sinusoidal tilts (from ~1 in 30s. to 1 in 3s.)

12. Session Description Preflight (II) • L-60 and L-10 lab session at Astronaut training center (20 min) • Cardiovascular reflex responses supine and upright paced breathing: • ~5 min supine baseline recording of Finapres blood pressure • 3*1 minute paced breathing at 6, 10, 15/min, 1 minute interval • ~5 min standing Finapres recording (hand at heart level) • 3*1 minute paced breathing at 6, 10, 15/min, 1 minute interval

13. Session DescriptionIn-Flight No in-flight experiments

14. Session DescriptionPostflight • R+0 • Usual flight-medical: stand test, after minimal upright G-loading; duration of orthostatic tolerance (up till 10 minutes) is used as ‘experiment outcome’. • R+1, R+5: (if this can be reconciled with the agenda) repeat of paced breathing tests

15. Experiment Training None

16. Possible Risks or Discomforts • Risks: • Orthostatic problems during the upright tests (dizziness, nausea, fainting if not moved back to supine); • Off nominal movements of the computer driven tilt table. • Discomforts: • Finger pain due to prolonged Finapres application; • Dryness of the mouth, due to test duration (total of 3 hours); • Pricking legs due to thigh cuff; • Tight fitting head band of the TCD-probe.

17. Experiment Benefits • Crewmember-specific countermeasures; • Spin-off for critical care use in clinical medicine; • To improve rehabilitation of patients after prolonged periods of bedrest.

18. Please refrain from smoking, drinking alcohol, and caffeinated drinks from 12 hrs before any recording Morning session: light breakfast Afternoon session: lunch 2 hrs before the start Protocol explanation

19. Finapres Continuous blood pressure measurement by means of a finger cuff A sling will support the hand to compensate for height differences Max. of 30 minutes finger blood pressure measurement to allow restoration of normal circulation Protocol explanation

20. TCD Blood flow velocity through the brain is measured by a TransCranial Doppler, applied to the side of the head with a headband Transmits low power ultrasound beam through skull ECG ECG electrodes will be applied to the chest to measure ECG and, in addition, chest fluid content Protocol explanation

21. Nostril clip to indicate respiration rhythm for paced breathing and measurement of expired CO2 to check for hyperventilation during paced breathing Blood pressure cuffs around the thighs to constitute a hindrance for venous blood return. Will be inflated temporarily Tilt table has foot and shoulder supports, and safety belts. Can be tilted swiftly and smoothly. Protocol explanation

22. The objective is to predict orthostatic intolerance due to microgravity during spaceflight. To make this prediction we test the astronauts/cosmonauts before their spaceflight in an elaborate (3 hr) test protocol on our Amsterdam computerized tilt table, while (non-invasively) measuring blood pressure, ECG and brain blood flow (by ultrasound) as main physiological parameters. This protocol is designed to categorize the cardiovascular reaction pattern of a person and act as predictor for the outcome of the test. As test outcome we use the normal stand test that is part of the medical check-up immediately after return. Astronauts are asked to stand relaxed, leaning against a wall or some other fixed object for a maximum of 10 minutes. Orthostatic intolerance is defined as the inability to stand for 10 minutes. The upright time before this test should be minimal, since hormonal re-adaptation to 1 G starts immediately after resumption of upright Earth-bound life. Summary