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Project Title:  Gender Differences in Bedrest: Autonomic and Neuroendocrine Changes and Vascular Responses in Lower and Upper Extremities Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 12/01/2006  
End Date: 06/30/2010  
Task Last Updated: 01/27/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Platts, Steven H. Ph.D. / NASA Johnson Space Center 
Address:  Cardiovascular Laboratory 
Biomedical Research and Environmental Sciences Division 
Houston , TX 77058 
Email: steven.platts-1@nasa.gov 
Phone: 281-483-8177  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: PI Steven Platts became PI 12/2006; see J. Meck for previous years' information on this project.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
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) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: NOTE: Changed end date to 6/30/2010 per PI information (jvp 8/19/10)

NOTE: Changed end date to 6/1/2010 due to PI information on hurricane delays in project; end date may change later (jvp 7/10/09)

Task Description: Women astronauts are more susceptible to postflight orthostatic hypotension and presyncope than are men. The reasons are not defined. Most bedrest studies that seek mechanisms of cardiovascular changes in response to microgravity have not included women. As a result, many conclusions about the effects of simulated microgravity on humans are flawed, in that they fail to describe mechanisms in the very people who have the most serious problems. We propose to determine how differences in strategies of arterial pressure control in men and women affect orthostatic tolerance both before and after bedrest. We will study endothelium-dependent, endothelium-independent and adrenergic receptor responses in both arteries and veins, before and after bedrest. In addition, we will measure plasma volumes, and hemodynamic and neuroendocrine responses to arterial and cardiopulmonary baroreceptor inputs, in women versus men, before and after bedrest. We also intend to pursue in humans the recent animal data which shows that different vascular beds respond differently to simulated microgravity. Hindlimb-suspended rats show hypertrophic remodeling of the vessels in their forelimbs and atrophic remodeling in the vessels of their hindlimbs. This is thought to occur because changes in transmural pressures and shear forces with hindlimb suspension occur in opposite directions in the upper and lower extremities. These studies have not been repeated in female rats, and nothing like this has been performed in humans of either gender. Since humans are bipedal, bedrest would greatly reduce transmural pressures and shear forces in the legs but not the arms. If vessel remodeling follows the patterns in humans as in the rats, large changes could occur which might contribute to orthostatic hypotension after bedrest. Accordingly, we plan to repeat the vascular measurements mentioned above in both upper and lower extremities before and after bed rest and relate the findings to the occurrence of orthostatic hypotension.

Research Impact/Earth Benefits: In addition to benefits for astronauts, millions of people on Earth suffer from orthostatic hypotension and may benefit from information gained from this experiment.

Task Progress & Bibliography Information FY2010 
Task Progress: Thirty-one (21 men, 11 women) subjects were studied during the course of this project. The purpose of this project was to examine the differences in the methods of blood pressure regulation in men and women, specifically the differences in the ways arteries, veins, and the heart work to control blood pressure. Furthermore, this study was conducted during 60 – 90 days of head down tilt bed rest, an analog for the cardiovascular deconditioning that occurs in astronauts during actual spaceflight, so differences between upper and lower body changes to bed rest were of significance.

The general results of this study indicated that men and women have some similar and some different methods of blood pressure regulation. Before bed rest, women had lower blood pressures than men and were more prone to develop orthostatic hypotension (extremely low blood pressure when standing up). However, both men and women had similar elevations of heart rate with bed rest and similar norepinephrine responses to standing. These results were expected, and the goals of this study were to examine the physiological mechanisms that might explain why women have a higher incidence of orthostatic intolerance.

Venous Function

Before bed rest, women had smaller veins in the feet than did men. After bed rest, women increased the size of these veins while men decreased the size of these veins. This, along with measures of strain gauge plethysmography, indicate that women increased their venous compliance while men did not, which would make women more susceptible to fainting than men. There were no differences between men and women in the response to drugs that affect the size of veins, such as phenylephrine, isoproterenol, acetylcholine or nitroglycerin.

Arterial Function

There were no arterial function differences between men and women, either before or during bed rest. However, this is the first study to show that upper and lower body arteries respond differently to bed rest. Ultrasound-measured arterial diameter showed decreases in the leg with bed rest, but not in the arm. Intima-medial thickness, the layer of the blood vessel wall that contains the smooth muscle which is responsible for controlling blood vessel constriction (and therefore blood pressure), decreased in the arteries of the leg, but not in the arm. Furthermore, responses to nitroglycerine, a measure of how well the smooth muscles in the artery walls are able to constrict or dilate, were reduced in the leg after bed rest, but not in the arm.

Baroreflex Function

Results from systemic infusions of phenylephrine and sodium nitroprusside, two agents that cause the blood vessels to constrict and relax, respectfully, were used to assess differences in baroreflex function. Women controlled their blood pressure more by utilizing changes in heart rate via the parasympathetic branch of the autonomic nervous system, while men exhibited greater sympathetic nervous system balance. Overall, baroreflex function was diminished with bed rest, but women had more of an attenuated baroreflex response than men, which may explain their predisposition to orthostatic intolerance.

The results of this study highlighted the differences in autonomic and baroreflex control of blood pressure regulation between men and women. Furthermore, changes in arterial structure and function were no different between men and women, although women developed a larger venous compliance after bed rest, while men did not.

Bibliography Type: Description: (Last Updated: 03/01/2018) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Stenger MB, Arzeno NM, Platts SH. "Baroreflex sensitivity decreases during 90-day bed rest." American College of Sports Medicine Annual Meeting, Seattle, WA, May 2009.

Medicine & Science in Sports & Exercise 2009 May;41(5 Suppl):59. http://dx.doi.org/10.1249/01.MSS.0000354743.59252.8b , May-2009

Articles in Peer-reviewed Journals Westby CM, Martin DS, Lee SM, Stenger MB, Platts SH. "Left ventricular remodeling during and after 60 days of sedentary head-down bed rest." J Appl Physiol (1985). 2016 Apr 15;120(8):956-64. Epub 2015 Oct 22. https://doi.org/10.1152/japplphysiol.00676.2015 ; PubMed PMID: 26494448; PubMed Central PMCID: PMC4835908 , Apr-2016
Project Title:  Gender Differences in Bedrest: Autonomic and Neuroendocrine Changes and Vascular Responses in Lower and Upper Extremities Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 12/01/2006  
End Date: 06/30/2010  
Task Last Updated: 07/10/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Platts, Steven H. Ph.D. / NASA Johnson Space Center 
Address:  Cardiovascular Laboratory 
Biomedical Research and Environmental Sciences Division 
Houston , TX 77058 
Email: steven.platts-1@nasa.gov 
Phone: 281-483-8177  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: PI Steven Platts became PI 12/2006; see J. Meck for previous years' information on this project.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
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) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: NOTE: Changed end date to 6/30/2010 per PI information (jvp 8/19/10)

NOTE: Changed end date to 6/1/2010 due to PI information on hurricane delays in project; end date may change later (jvp 7/10/09)

Task Description: Women astronauts are more susceptible to postflight orthostatic hypotension and presyncope than are men. The reasons are not defined. Most bedrest studies that seek mechanisms of cardiovascular changes in response to microgravity have not included women. As a result, many conclusions about the effects of simulated microgravity on humans are flawed, in that they fail to describe mechanisms in the very people who have the most serious problems. We propose to determine how differences in strategies of arterial pressure control in men and women affect orthostatic tolerance both before and after bedrest. We will study endothelium-dependent, endothelium-independent and adrenergic receptor responses in both arteries and veins, before and after bedrest. In addition, we will measure plasma volumes, and hemodynamic and neuroendocrine responses to arterial and cardiopulmonary baroreceptor inputs, in women versus men, before and after bedrest. We also intend to pursue in humans the recent animal data which shows that different vascular beds respond differently to simulated microgravity. Hindlimb-suspended rats show hypertrophic remodeling of the vessels in their forelimbs and atrophic remodeling in the vessels of their hindlimbs. This is thought to occur because changes in transmural pressures and shear forces with hindlimb suspension occur in opposite directions in the upper and lower extremities. These studies have not been repeated in female rats, and nothing like this has been performed in humans of either gender. Since humans are bipedal, bedrest would greatly reduce transmural pressures and shear forces in the legs but not the arms. If vessel remodeling follows the patterns in humans as in the rats, large changes could occur which might contribute to orthostatic hypotension after bedrest. Accordingly, we plan to repeat the vascular measurements mentioned above in both upper and lower extremities before and after bed rest and relate the findings to the occurrence of orthostatic hypotension.

Research Impact/Earth Benefits: During this research new protocols have been developed to study vascular responses. These new protocols will help determine the components of acetylcholine-mediated vasodilation in both normal and disease states. This protocol will also help determine the importance of the renin-aldosterone system in male and female responses to dehydration.

Task Progress & Bibliography Information FY2009 
Task Progress: To date, 32 subjects (12 females, 20 males) have been enrolled in the study. Of those, only 15 subjects (5 females, 10 males) have completed the full protocol. Those subjects who did not complete the full protocol were, by in large, released early due to Hurricane Ike (2008). As such, the results are based on data analyzed to date on 5 females and 10 males. These initial results, while not complete and underpowered, do appear to support our general hypothesis that there are many cardiovascular differences with bedrest between males and females.

Bibliography Type: Description: (Last Updated: 03/01/2018) 

Show Cumulative Bibliography Listing
 
 None in FY 2009
Project Title:  Gender Differences in Bedrest: Autonomic and Neuroendocrine Changes and Vascular Responses in Lower and Upper Extremities Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 12/01/2006  
End Date: 06/01/2009  
Task Last Updated: 04/10/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Platts, Steven H. Ph.D. / NASA Johnson Space Center 
Address:  Cardiovascular Laboratory 
Biomedical Research and Environmental Sciences Division 
Houston , TX 77058 
Email: steven.platts-1@nasa.gov 
Phone: 281-483-8177  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: PI Steven Platts became PI 12/2006; see J. Meck for previous years' information on this project.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
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) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Task Description: Women astronauts are more susceptible to postflight orthostatic hypotension and presyncope than are men. The reasons are not defined. Most bedrest studies that seek mechanisms of cardiovascular changes in response to microgravity have not included women. As a result, many conclusions about the effects of simulated microgravity on humans are flawed, in that they fail to describe mechanisms in the very people who have the most serious problems. We propose to determine how differences in strategies of arterial pressure control in men and women affect orthostatic tolerance both before and after bedrest. We will study endothelium-dependent, endothelium-independent and adrenergic receptor responses in both arteries and veins, before and after bedrest. In addition, we will measure plasma volumes, and hemodynamic and neuroendocrine responses to arterial and cardiopulmonary baroreceptor inputs, in women versus men, before and after bedrest. We also intend to pursue in humans the recent animal data which shows that different vascular beds respond differently to simulated microgravity. Hindlimb-suspended rats show hypertrophic remodeling of the vessels in their forelimbs and atrophic remodeling in the vessels of their hindlimbs. This is thought to occur because changes in transmural pressures and shear forces with hindlimb suspension occur in opposite directions in the upper and lower extremities. These studies have not been repeated in female rats, and nothing like this has been performed in humans of either gender. Since humans are bipedal, bedrest would greatly reduce transmural pressures and shear forces in the legs but not the arms. If vessel remodeling follows the patterns in humans as in the rats, large changes could occur which might contribute to orthostatic hypotension after bedrest. Accordingly, we plan to repeat the vascular measurements mentioned above in both upper and lower extremities before and after bed rest and relate the findings to the occurrence of orthostatic hypotension.

Research Impact/Earth Benefits: During this research new protocols have been developed to study vascular responses. These new protocols will help determine the components of acetylcholine-mediated vasodilation in both normal and disease states. This protocol will also help determine the importance of the renin-aldosterone system in male and female responses to dehydration.

Task Progress & Bibliography Information FY2007 
Task Progress: NOTE: PI change effective 12/1/2006--see PI Steven Platts for continuation information for this task (note added 4/2008)

Bibliography Type: Description: (Last Updated: 03/01/2018) 

Show Cumulative Bibliography Listing
 
 None in FY 2007