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Principal Investigator:
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Benjamin D. Levine, M.D.
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Organization:
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The University of Texas Southwestern Medical Center at Dallas
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Some long-duration astronauts have had diminished visual acuity during and after spaceflight. Serious visual impairment is not only problematic for an individual astronaut, but may be mission threatening for a long-duration crew. The mechanism(s) causing this problem remain largely unknown. The current working model is that it may be related to changes in intracranial pressure (ICP) due to fluid shifts in microgravity, perhaps exacerbated by small increases in the pCO2 or by exercise. However, only a few in-flight (ultrasound) and post-flight (MRI and lumbar puncture) observations support this contention. The only way to obtain this knowledge with certainty is to directly measure ICP during relevant changes in hydrostatic gradients. Importantly, these measures must be made in concert with an evaluation of inflow (arterial) and outflow (venous) pressures and flows to better understand intracranial hemodynamics in space.
The primary objective of this project is to directly measure intracranial pressure, cerebral hemodynamics and structure of the visual apparatus during changes in hydrostatic gradients (parabolic flight) that mimic microgravity exposure.
Hypotheses
1) The transition from the upright to the supine posture increases intracranial and right atrial pressures without a clinically significant change in ocular structure. The location of the intracranial hydrostatic indifference point (where rotation around that Gy axis in the Gz plane causes no change in hydrostatic pressure) determines the magnitude of the increase in ICP during changes in posture and in microgravity. If so, this characteristic could be a testable risk factor for visual impairment in space.
2) Microgravity-induced changes (via parabolic flight) in cerebral pressures and flow will be greater than those observed during bed rest.
Specific Aims
1) The researchers will recruit adult patients that, because of prior medical treatment, have a brain access port from which ICP can be measured with little risk to the patient. Importantly, the selected patients will have no intracranial or cardiovascular pathology, and thus ICP can be measured accurately. Simultaneous measurement of right atrial pressure and arterial pressure will be combined with echo/Doppler measures of the middle cerebral artery, carotid and jugular vessels, and ocular ultrasound for globe size, shape and optic sheath diameter during 24 hours of head-down-tilt bed rest. These measures will allow a comprehensive assessment of cerebrovascular hemodynamics during routine gravitational transients. The hydrostatic indifference point will be determined in each volunteer. Additional measurements will be made with modest increases in carbon dioxide concentrations, and during strength exercise to determine the independent and additive effects of these confounding stimuli.
2) Subjects from Specific Aim 1 will be exposed to parabolic flight (on a separate day) to achieve brief periods of microgravity. This protocol will allow comparison between real microgravity, and usual terrestrial changes in hydrostatic gradients during daily life (e.g., from supine to upright). Similar to Aim 1, measurements will be obtained at rest, during exercise, and during small increases in carbon dioxide concentrations (10 parabolas each).
The study of intracranial and cardiocerebral hemodynamics in microgravity has been largely unexplored. Only a careful dissection of the pathophysiology will allow the development of effective countermeasures that could ultimately lead to reducing the risk of visual impairments during spaceflight. Thus, this project will serve as the essential science base required to address a potential critical impediment to safe, long-duration spaceflight.
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