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Project Title:  Determining the Dose Response Profile of the Headward Fluid Shift during Varying Gravity Levels Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2021  
End Date: 02/29/2024  
Task Last Updated: 02/03/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Martin, David  M.S. KBR/NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Macias, Brandon  Ph.D. NASA Johnson Space Center 
Marshall-Goebel, Karina  Ph.D. KBR/NASA Johnson Space Center 
Young, Millennia  Ph.D. NASA Johnson Space Center 
Besnard, Stephane  M.D., Ph.D. University Hospital of Caen, France 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) CVD:Risk of Spaceflight Induced Cardiovascular Disease (IRP Rev L)
(2) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) SANS-301:Laboratory development of mechanical countermeasures (IRP Rev L)
Task Description: Long-duration stays in weightlessness have resulted in changes in the function and structure of the eye in some astronauts which has been described as Spaceflight-Associated Neuro-ocular Syndrome (SANS). The leading hypothesis is that ocular changes associated with SANS result from chronic exposure to the weightlessness-induced headward fluid shift. The resulting venous congestion in the upper body may impair cerebrospinal and lymphatic fluid drainage from the skull and contribute to some of the changes in the eye. Further, venous stasis may develop in some astronauts, increasing the risk of a venous thrombus. Countermeasures that reverse the headward fluid shift during spaceflight such as centrifugation or lower body negative pressure have been proposed as means to relieve venous congestion associated with weightlessness and thus may mitigate the risk of SANS, venous thrombosis, and other spaceflight-induced cardiovascular adaptations. However, the amount of fluid shift reversal required to prevent SANS, venous thrombosis, and cardiovascular adaptations is unresolved. Parabolic flight provides a unique opportunity to evaluate the acute changes in the headward fluid shift within the venous compartment induced by varying levels of gravity during partial gravity and weightlessness.

The primary task objectives are to determine whether exposures to partial gravity levels (G-levels) similar to extraterrestrial levels (Moon and Mars) will provide protection against the headward fluids shifts that may be associated with the development of SANS, venous thromboembolism (VTE), and cardiovascular deconditioning. With the results from this partial gravity parabolic campaign, we will provide additional data that will contribute to comprehensive models of the relationship between G-levels and internal jugular vein (IJV) dimensions, pressure, and flow. Furthermore, investigating IJV hemodynamics bilaterally and studying the IJV in these subjects during parabolas producing weightlessness will better inform NASA regarding the risk of SANS and venous thrombosis and aid in the development of appropriate countermeasures.

Specific Aims

1. Determine the relationship between G-level and upper body venous hemodynamic parameters associated with a headward fluid shift, including IJV pressure, flow pattern, and cross-sectional area.

2. Determine if the relationship between G-level and upper body venous hemodynamic parameters is different between the left and right sides of the body.

3. Determine whether the supine posture in normal gravity produces similar internal jugular vein hemodynamics as occurs in acute weightlessness.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research. This work was recommended by the Human Health Countermeasures (HHC) element to be performed as a directed study (a) to fulfill the partial gravity flight campaign human data collection objectives outlined in the previously-selected NASA Research Announcement (NRA; NNJ15ZSA001N-AG); (b) to provide the necessary data to accelerate HHC Spaceflight Associated Neuro-ocular Syndrome (SANS) risk reduction; and (c) to provide the necessary headward fluid shift data to help inform requirements for future lunar (Artemis Program) and Mars exploration. This proposed task will allow Human Research Program (HRP) to take advantage of a planned European Space Agency (ESA)-sponsored partial gravity parabolic flight opportunity in Spring or Summer of 2022. Furthermore, utilizing the same study design and outcome measures as the first campaign will ensure data consistency, enable us to leverage previously-developed human research documentation, hardware, and engineering analyses required by the parabolic flight provider (cost efficiency).

When our first study was selected as part of a NASA Research Announcement (NRA) (NNJ15ZSA001N-AG), the power analysis indicated that data should be collected from 15 subjects. However, the ESA parabolic flight plan limited data collection to 9 subjects. Due to technical constraints and reduced operator support in the first campaign, internal jugular vein (IJV) area was obtained in only 8 of 9 subjects and IJV pressure only in 3 subjects at the lower G-levels. Thus, collecting data from 9 additional subjects as outlined here will allow us to fully explore the threshold G-level required to prevent venous congestion (IJV area and pressure) and altered flow patterns. In addition, this will allow us to assess the effects of right vs. left IJV anatomy on IJV dimension, pressure, and flow to varying G-levels, which has not been previously explored and may be key in assessing SANS and thrombosis risks. Finally, the previous partial gravity parabolic flight campaign did not include parabolas producing weightlessness, and thus the previous dose-response curves describing the relationship between G-level and IJV area required the assumption that IJV dimensions in the supine posture was a suitable analog. With the addition of weightlessness parabolas in a new campaign, this approach will be validated. Data from this project also will complement the weightless parabolic flight study recently funded for our laboratory (Characterization of Jugular Venous Blood Flow during Acute Fluid Shifts, Principal Investigator: Karina Marshall-Goebel, Ph.D., 80JSC019N0001-OMNIBUS - HERO Appendix B: NASA Human Research Program Omnibus Opportunity).

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2022 
Task Progress: The overall objective of this study is to characterize the relationship between gravity levels (G-levels) and acute changes in the internal jugular vein (IJV) pressure, cross-sectional area, and flow using ultrasound. Beat-to-beat finger blood pressure and heart rate from a 3-lead electrocardiogram (ECG) configuration also will be acquired. Our previous spaceflight study (Fluid Shifts) revealed IJV expansion and altered flow during long-duration spaceflight, as well as the presence of a thrombus in one astronaut, when measurements were obtained from the left IJV. However, in our previous parabolic flight campaign, we only examined the right IJV. Clinically IJV flow reversal is most commonly reported to occur in the left IJV, likely due to anatomical differences between the left and right IJV and brachiocephalic veins. Thus, here we will obtain IJV measurements bilaterally. Specifically, we will characterize the IJV changes during different levels of gravity and hydrostatic gradients (Gz), including preflight supine (0-G analog), 0.25-, 0.50-, 0.75 and 0-G while seated during parabolic flight, and 1-G seated during level flight between parabolas.

No results are available currently. The parabolic flight campaign is tentatively scheduled for June 2023.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee SMC, Martin DS, Laurie SS, Lytle J, Marshall-Goebel K, Miller CA, Young M, Besnard S, Macias BR. "Determining dose response profile of the headward fluid shift during varying gravity levels." 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022 (Abstract #1133-000530). , Feb-2022

Project Title:  Determining the Dose Response Profile of the Headward Fluid Shift during Varying Gravity Levels Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2021  
End Date: 02/29/2024  
Task Last Updated: 05/20/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Martin, David  M.S. KBR/NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Macias, Brandon  Ph.D. NASA Johnson Space Center 
Marshall-Goebel, Karina  Ph.D. KBR/NASA Johnson Space Center 
Young, Millennia  Ph.D. NASA Johnson Space Center 
Besnard, Stephane  M.D., Ph.D. University Hospital of Caen, France 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) CVD:Risk of Spaceflight Induced Cardiovascular Disease (IRP Rev L)
(2) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) SANS-301:Laboratory development of mechanical countermeasures (IRP Rev L)
Task Description: Long-duration stays in weightlessness have resulted in changes in the function and structure of the eye in some astronauts which has been described as Spaceflight-Associated Neuro-ocular Syndrome (SANS). The leading hypothesis is that ocular changes associated with SANS result from chronic exposure to the weightlessness-induced headward fluid shift. The resulting venous congestion in the upper body may impair cerebrospinal and lymphatic fluid drainage from the skull and contribute to some of the changes in the eye. Further, venous stasis may develop in some astronauts, increasing the risk of a venous thrombus. Countermeasures that reverse the headward fluid shift during spaceflight such as centrifugation or lower body negative pressure have been proposed as means to relieve venous congestion associated with weightlessness and thus may mitigate the risk of SANS, venous thrombosis, and other spaceflight-induced cardiovascular adaptations. However, the amount of fluid shift reversal required to prevent SANS, venous thrombosis, and cardiovascular adaptations is unresolved. Parabolic flight provides a unique opportunity to evaluate the acute changes in the headward fluid shift within the venous compartment induced by varying levels of gravity during partial gravity and weightlessness.

The primary task objectives are to determine whether exposures to partial gravity levels (G-levels) similar to extraterrestrial levels (Moon and Mars) will provide protection against the headward fluids shifts that may be associated with the development of SANS, venous thromboembolism (VTE), and cardiovascular deconditioning. With the results from this partial gravity parabolic campaign, we will provide additional data that will contribute to comprehensive models of the relationship between G-levels and internal jugular vein (IJV) dimensions, pressure, and flow. Furthermore, investigating IJV hemodynamics bilaterally and studying the IJV in these subjects during parabolas producing weightlessness will better inform NASA regarding the risk of SANS and venous thrombosis and aid in the development of appropriate countermeasures.

Specific Aims

1. Determine the relationship between G-level and upper body venous hemodynamic parameters associated with a headward fluid shift, including IJV pressure, flow pattern, and cross-sectional area.

2. Determine if the relationship between G-level and upper body venous hemodynamic parameters is different between the left and right sides of the body.

3. Determine whether the supine posture in normal gravity produces similar internal jugular vein hemodynamics as occurs in acute weightlessness.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research. This work was recommended by the Human Health Countermeasures (HHC) element to be performed as a directed study (a) to fulfill the partial gravity flight campaign human data collection objectives outlined in the previously-selected NASA Research Announcement (NRA; NNJ15ZSA001N-AG); (b) to provide the necessary data to accelerate HHC Spaceflight Associated Neuro-ocular Syndrome (SANS) risk reduction; and (c) to provide the necessary headward fluid shift data to help inform requirements for future lunar (Artemis Program) and Mars exploration. This proposed task will allow Human Research Program (HRP) to take advantage of a planned European Space Agency (ESA)-sponsored partial gravity parabolic flight opportunity in Spring or Summer of 2022. Furthermore, utilizing the same study design and outcome measures as the first campaign will ensure data consistency, enable us to leverage previously-developed human research documentation, hardware, and engineering analyses required by the parabolic flight provider (cost efficiency).

When our first study was selected as part of a NASA Research Announcement (NRA) (NNJ15ZSA001N-AG), the power analysis indicated that data should be collected from 15 subjects. However, the ESA parabolic flight plan limited data collection to 9 subjects. Due to technical constraints and reduced operator support in the first campaign, internal jugular vein (IJV) area was obtained in only 8 of 9 subjects and IJV pressure only in 3 subjects at the lower G-levels. Thus, collecting data from 9 additional subjects as outlined here will allow us to fully explore the threshold G-level required to prevent venous congestion (IJV area and pressure) and altered flow patterns. In addition, this will allow us to assess the effects of right vs. left IJV anatomy on IJV dimension, pressure, and flow to varying G-levels, which has not been previously explored and may be key in assessing SANS and thrombosis risks. Finally, the previous partial gravity parabolic flight campaign did not include parabolas producing weightlessness, and thus the previous dose-response curves describing the relationship between G-level and IJV area required the assumption that IJV dimensions in the supine posture was a suitable analog. With the addition of weightlessness parabolas in a new campaign, this approach will be validated. Data from this project also will complement the weightless parabolic flight study recently funded for our laboratory (Characterization of Jugular Venous Blood Flow during Acute Fluid Shifts, Principal Investigator: Karina Marshall-Goebel, Ph.D., 80JSC019N0001-OMNIBUS - HERO Appendix B: NASA Human Research Program Omnibus Opportunity).

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2021 
Task Progress: New project for FY2021.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
 None in FY 2021