Cerebral and Ocular Fluid Balance as a Function of Space-Related Environmental Factors: Insights into Visual Impairment in Astronauts

The visual impairment and intracranial pressure (VIIP) syndrome affects more than half of astronauts during 6-month missions on the International Space Station (ISS) resulting in significant structural and functional ophthalmic changes. Although the exact pathophysiological mechanisms underlying the ocular changes are unknown, headward fluid shifting due to the absence of gravity and subsequent alterations in cerebral hemodynamics and intracranial pressure (ICP) may play a major role. The overarching aim of this thesis was to elucidate the effects of cephalad fluid shifting during head-down tilt (HDT), commonly used as a spaceflight analog model, on cerebral and ocular anatomy and physiology. As a secondary aim, the potential additive effects of increased ambient carbon dioxide (CO2) during HDT were assessed as well as the ability of lower body negative pressure (LBNP) to counteract headward fluid shifting. The scope of the PhD thesis work was split into three main studies. In the first study, cerebral as well as ocular fluid and pressure balance was assessed during 5 h HDT exposure in 5 experimental conditions: -6°, -12° and -18° HDT, -12° with 1% CO2 and -12° HDT with -20 mmHg LBNP. Thereafter, the second study investigated a longer duration exposure to -12° HDT (29 h) with and without increased ambient CO2. Finally, the third study tested the effects of stronger LBNP (-40 mmHg) for shorter durations of time with an extended range of tilt angles. The results show that HDT leads to signs of cerebral venous congestion demonstrated by the large increase in internal jugular vein cross-sectional area and decreased cerebral venous outflow. Furthermore, HDT induced increases in intracranial as well as periorbital cerebrospinal fluid (CSF) volume, consistent with decreased CSF absorption due to elevated cerebral venous pressure. Intraocular pressure (IOP) remained greater than ICP during HDT, resulting in a small, positive intraocular-intracranial pressure difference (IOP > ICP) during both acute and overnight HDT, contrary to the hypothesized shift to a greater ICP. In addition, exposure to increased ambient CO2 on the ISS was hypothesized to be a contributing factor to the ocular changes in astronauts by further increasing intracranial blood volume and therefore pressure. In combination with HDT, exposure to elevated ambient CO2 increased cerebral blood flow and venous outflow, however, had little additive effect on IOP or ICP during acute or longer-duration exposure.2 Alterations in cerebral hemodynamics secondary to headward fluid shifting are central to the hypothesized mechanisms underlying the VIIP syndrome and may induce a cascade of ophthalmic changes over long-duration exposure. Finding a way to mitigate vision changes in space is vital to ensure long-duration exploration class mission feasibility and success. Therefore, LBNP, a technique that redistributes venous blood volume to the lower limbs, was tested as a mechanical countermeasure to cephalad fluid shifting. Notably, low-level LBNP (-20 mmHg) during -12° HDT was able to successfully attenuate the HDT-induced increase in periorbital as well as intracranial CSF volume. Although -20 mmHg LBNP had no effect on IOP or ICP, exposure to - 40 mmHg LBNP was able to attenuate HDT-induced increases in IOP during a range of tilt angles. Overall, the presented studies represent novel investigations into the cerebral and ocular effects of various degrees of cephalad fluid shifting as well as the unique combination of HDT and increased ambient CO2 as a more realistic analog of the ISS environment. Impediment of venous return by LBNP was also established as a promising technique to counteract cephalad fluid shifting and redistribute CSF and may be able prevent future development of structural ocular changes associated with the VIIP syndrome. These studies have contributed to the further understanding of potential mechanisms involved in the development of ocular changes in astronauts, notably the central role of cerebral hemodynamics and cerebral venous congestio