Exposure to weightlessness results in the removal of hydrostatic pressure gradients and a permanent headward fluid shift, causing a redistribution of blood. Additionally, in space postural changes don’t occur and thus, astronauts are not exposed to daily fluid shifts (between supine and upright postures) as we are on Earth. This has currently unknown consequences, but it might be related to a series of neuro-ocular and functional changes developed in some astronauts during both short and long-duration spaceflight, collectively known as Spaceflight Associated Neuro-Ocular Syndrome (SANS). While the exact etiology of SANS is currently unknown, chronic fluid redistribution affecting intravascular, interstitial, and cerebrospinal fluids and pressures is widely hypothesized to be a contributing factor. Additionally, recently demonstrated stagnant and retrograde blood flow and venous thrombosis in the left internal jugular vein during spaceflight could also be associated with sustained headward blood and tissue fluid shift.
Based on the current knowledge and hypotheses, countermeasures focused on producing hydrostatic gradients or reducing the microgravity-induced fluid shift, such as lower body negative pressure (LBNP) or centrifugation, become particularly interesting. LBNP shifts fluids from the head to the lower body is expected to reduce the translaminar pressure across the eye and thus, might prevent some of the ocular changes and remodeling associated with SANS. LBNP is also a promising countermeasure to enhance venous flow in the upper body. Similarly, head-to-foot (Gz) centrifugation also produces a fluid shift and induces hydrostatic gradients within the vessels in the body, which may also reduce intraocular pressure (IOP), reduce the translaminar pressure, and enhance venous flow. However, at present, it is not possible to estimate the overall physiological response (neither acute nor long term) of a particular “dose” of artificial gravity (AG) or LBNP, and more specifically and relevant to our purposes, the response in the upper body and around the eye. As a first step and in the context of this short project, we propose to focus on acute responses. Our objective is to generate acute gravitational dose-response curves of cardiovascular (CV) and ocular variables due to changes in the gravitational vector, with and without countermeasures. We propose to conduct a series of experimental studies (using tilt table, LBNP, and centrifugation), and combine the results with numerical modeling to leverage the advantages of both experimental and computational methodologies. Then, we propose to exert the full flexibility of the numerical framework to investigate CV and ocular responses in additional configurations where data collection is difficult, expensive, or infeasible.
A short-description of the experiments is shown below:
- Experiment 1: Tilt table. Subjects will be exposed to multiple tilt angles, from 45° HUT (head up tilt) to 45° HDT (head down tilt), in both prone and supine configurations. CV and ocular measures will be collected and used to generate gravitational dose-response curves as a function of tilt angle.
- Experiment 2: LBNP. Subjects will be exposed to multiple levels of negative pressure (from 0 to -50 mmHg), in both supine and 15° HDT. Similarly, CV and ocular measures will be collected and used to generate gravitational dose-response curves as a function of external pressure.
- Experiment 3: Centrifugation. Subjects will be exposed to multiple levels of artificial gravity on the human short-radius NASA centrifuge that is being relocated and installed at Texas A&M University (TAMU). CV and ocular measures will be collected and used to generate gravitational dose-response curves as a function of g-level.
In addition to the experiments, we will develop a numerical model from two different but complementary lumped-parameter models that have been previously validated and published in the literature: 1) A full-body model that provides an accurate simulation of short-term CV regulatory changes during changes in the gravitational vector (i.e., different tilt angles, centrifugation) and countermeasures (i.e., LBNP, exercise). This model features a more accurate body representation, including a cardiac pacemaker (i.e., pulsatile waveform), baroreceptor and cardiopulmonary feedback control of heart and arterial parameters, and a large number of compartments, particularly in the Gz direction, allowing for an improved representation of hydrostatic gradients in this direction and overall body hemodynamics. 2) An eye model that simulates volume/pressure alterations in the eye during gravitational changes. We will combine both approaches leveraging the advantages of each one of them into a unique more powerful and versatile model to study SANS, the cranial venous system, and other fluid shifts mechanisms and the effects of potential countermeasures. The model will be validated with the experimental data generated during the experiments.
Results from this investigation will inform current and future countermeasure development and in-flight prescriptions.
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