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Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 10/01/2015  
Task Last Updated: 07/13/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Scheer, Frank  Ph.D. Brigham And Women's Hospital, Inc. 
Matthew, Butler  Ph.D. Brigham and Women's Hospital, Inc. 
Barr, David  Ph.D. Brigham and Women's Hospital, Inc. 
Crucian, Brian E Ph.D. NASA-Johnson Space Center/Wyle Life Sciences Group 
Mehta, Satish K Ph.D. NASA-Johnson Space Center/Wyle Life Sciences Group 
Rueger, Melanie  Ph.D. Brigham and Women’s Hospital, Inc. 
Pierson, Duane L Ph.D. NASA-Johnson Space Center/Wyle Life Sciences Group 
Hu, Kun  Ph.D. Brigham and Women’s Hospital, Inc. 
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 9/30/2015, per PI and NSSC information (Ed., 8/5/14)

Task Description: This project investigated the impact of sleep loss and circadian disruption on the cardiovascular (CV) system, including the CV responses to mental and physical challenges that are commonly encountered during space flight.

Microgravity affects CV function by decreasing circulating blood volume and central venous blood pressure and increasing stroke volume and cardiac output, potentially leading to cardiac rhythm disturbances, which have been documented during spaceflight [1]. On top of this, astronauts experience additional CV stress, for example, during space walks or robotic operations during Extravehicular Activities (EVAs) [2]. In addition, during any space mission, astronauts experience unusual light-dark cycles (currently the 90 min cycle on board of the ISS) [3] leading to some degree of chronic circadian disruption which can take the form of: (a) the whole body being at the ‘wrong time’ given the prevailing behaviors. For example, astronauts are often awake, eat and perform activities at the time when their internal biological clocks are preparing the body for optimal physiological rest and sleep; or they may be trying to sleep during the biological day when their circadian clock normally prepares the body for activities; or (b) parts of the body can be set to suboptimal times, such ‘internal desynchrony’ when varied cells and organs are shifting to new time zones at different rates. Thus, circadian disruption may result in maladaptive physiological responses. In addition, the inevitable sleep loss that accompanies circadian disruption itself can further stress the CV system. Undoubtedly, mission requirements, such as ‘slam shifting’ before EVAs and working extended shifts during EVAs will contribute to sleep loss. The environmental conditions on the International Space Station (ISS), e.g., noise, and heat, also contribute to sleep loss. Data from laboratory and epidemiological studies have shown that unfavorable changes in endocrine, inflammatory, and CV function occur in individuals as a result of chronic sleep restriction [4] and circadian disruption [5, 6]; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope [7], hypertension, diabetes, and metabolic syndrome. With the possibility of longer space exploration missions in the future, the effect of sleep loss and circadian disruption on health, performance and safety is paramount. Adverse CV events can be triggered by numerous stressors (e.g., exercise, sleep loss, circadian disruption) causing changes in CV risk markers, such as increased blood pressure, cardiac vagal withdrawal, sympathetic activation, and promotion of hemostatic mechanisms.

Cardiac arrhythmias have been observed in astronauts and are considered a major risk endangering the success of space missions [8]. In addition to structural changes, such arrhythmias can be triggered by numerous interacting and summating stressors [9, 10] (e.g., exercise, sleep loss, working during the biological night [‘circadian disruption’]) causing changes in cardiovascular risk markers, such as increased blood pressure, cardiac vagal withdrawal, sympathetic activation, and promotion of hemostatic mechanisms. While such responses can be vital homeostatic responses to such challenges, chronic activation of these mechanisms, or activation in individuals with underlying susceptibilities (e.g., with possibly sub-clinical but vulnerable atherosclerotic plaques) can be counterproductive and lead to adverse cardiovascular events, including stroke or myocardial infarction [9, 11].

Therefore, the aims of this project were to identify, in ostensibly healthy individuals of a similar age range as astronauts, the influences of sleep loss and circadian disruption on CV responses to physiological stresses that may occur throughout long missions. Characterizing these effects may help us determine if countermeasures would be recommended in order to limit adverse CV effects during long and short duration space missions.

SPECIFIC AIMS:

1. The effect of circadian disruption on CV function, including the CV responses to physical and mental challenges commonly encountered during spaceflight.

2. The effect of sleep loss on CV function, including the CV responses to physical and mental challenges commonly encountered during spaceflight.

3. The synergetic effects of circadian disruption plus sleep loss on CV function, including the CV responses to physical and mental challenges commonly encountered during spaceflight.

Our studies of sleep and circadian stressors on cardiovascular performance are relevant to astronauts in spaceflight as well as the many workers on Earth who experience similar conditions, albeit with gravity, during shift work.

NOTE: References available in the Task Progress section below.

Research Impact/Earth Benefits: Research Impact:

Astronauts experience circadian misalignment, sleep loss, and different mental and physical stressors during missions; it is possible that these conditions contribute to sub-optimal cardiovascular function and that these effects will be exacerbated by stressors such as exercise during EVAs and postural stresses on return to Earth. Nevertheless, to date, we have little-to-no knowledge about how the relevant hemodynamic, autonomic, hemostatic, vascular, and endothelial biomarkers that comprise our dependent variables, react to simultaneous challenging circumstances of circadian misalignment, sleep loss and physical or mental exertion/stress. Once the effects of circadian misalignment, sleep loss, and different stressors are determined and vulnerable periods are identified, we hope to develop measures to alleviate or limit the risks by both ensuring proper circadian entrainment and sleep, and by ensuring activities that particularly challenge the cardiovascular system are avoided at specific vulnerable states of circadian misalignment and sleep loss. This could inform a new gap related to ‘inter-individual vulnerabilities’ to challenging work environments, including countermeasures and improvements of already existing challenging work environments (spaceflight and shift work), and better screening tools for future employees experiencing these work environments.

The research project has considerable relevance to a number of parts of NASA’s current Human Research Program (HRP) Integrated Path to Risk Reduction. In the HRP element of Human Health Countermeasures (HHC), the research is relevant to the following risks:

1. Arrhythmia: Risk of Cardiac Rhythm Problems;

2. Immune: Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F) In the HRP element of Behavioral Health and Performance (BHP), the research is relevant to the following risk:

3. Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

The research has relevance to the following specific HRP gaps:

CV01: What are the in-flight alterations in cardiac structure and function?

CV03: Is orthostatic intolerance a potential hazard?

CV08: Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?

IM03: We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E).

IM08: We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E).

Sleep 2: We need to understand the contribution of sleep loss, circadian desynchronization, extended wakefulness, and work overload on individual health (physical and behavioral), team functioning, and performance (including operational performance), for spaceflight.

Sleep 4: We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions.

Sleep 10: We need to identify the spaceflight environmental and mission factors that contribute to sleep decrements and circadian misalignment, and their acceptable levels of risk.

Earth Benefits:

Curtailed sleep and circadian disruptions are common features of modern life, on Earth as well as in space. Night-shift work is common among factory workers, police, fire fighters, and nurses, and such work has been identified as a risk factor for a host of diseases, including cardiovascular disease, stroke, and metabolic disorders. Our work therefore stands to impact health in astronauts, health in workers on Earth, and may point to countermeasures and improvements in work-schedule design.

Task Progress & Bibliography Information FY2016 
Task Progress: To address the aims we studied volunteer healthy participants throughout two 11-day ‘inpatient’ protocols that combined circadian disruption with extended sleep opportunity (i.e., sufficient sleep) or short sleep (i.e., insufficient sleep). We sought healthy, non-obese, habitually active, male and female volunteers, aged 35-55 years, with no history of chronic medical disorders, no medications, and no substance abuse. This profile was designed to emulate the typical astronaut crew profile. Planned enrollment was 16 participants (8 male, 8 female). Based on flyers, plus newspaper, transportation and web based advertising, we received 2148 inquires. Overall 14 healthy, habitually active participants completed all of the screening and both of the in-laboratory phases of the study (8 male; 6 female).

Each participant was studied in both the Short Sleep and Long Sleep conditions (randomized). These two protocols were called ‘forced desynchrony’ protocols because the day length was shorter than 24 hours (h) such that the behavioral rest/activity cycle became desynchronized from the internal circadian cycle. This was achieved by scheduling participants to live on recurring 20 h ‘days’ in dim light (<3 lux), allowing the endogenous circadian pacemaker to oscillate at its inherent period rather than being reset by daily exposure to the light-dark cycle [12]. One protocol (Short Sleep) permitted sleep for 5 h per 20 h ‘day’, which is equivalent to 6 h sleep opportunity per 24 h for an entire week. The other protocol (Long Sleep) allowed 8 h 20 min sleep per 20 h-‘day’, which is equivalent to 10 h sleep opportunity per 24 h for an entire week. This approach allows us to uniformly distribute the sleep/wake cycle across the circadian cycle to quantify the independent influences of the circadian system and behaviors and also their interacting effects. Under these carefully controlled conditions we tested the hypothesis that circadian disruption combined with sleep restriction would result in unfavorable changes in cardiovascular (CV) function during behavioral challenges commonly faced by astronauts. A behavioral test battery was performed at the same time relative to time since scheduled waking during each laboratory protocol (starting at 2 h after scheduled wake time). Before each test battery, participants had been supine for at least 5 h during the sleep periods in both the Long Sleep and Short Sleep conditions. Subsequently, when lights were switched from darkness to the dim light condition (3 lux), participants remained in a semi-recumbent posture (upper body at 45º) for 2 h during which time they were provided with a urinal or bedpan as needed. During this time participants consumed breakfast 1 h after scheduled wake time. An identical behavioral test battery was repeated on each 20 h ‘day’ and included three standardized stressors performed in the following order: (i) a mental challenge; (ii) a postural challenge; and (iii) an exercise stressor.

Physiological Measurements

In brief, the following dependent variables were assessed at the beginning and at the end of each protocol (i.e., without and with sleep loss, and before and after circadian disruption):

• Maximal oxygen consumption (incremental treadmill exercise to maximal tolerable level

• Hemodynamic response to a strong postural challenge (passive 80° head-up tilt for 30 minutes)

• Cardiac structure and function (echocardiography)

• Endothelial function (reactive hyperemia index and endothelial-independent vasodilation)

• ECG arrhythmias (24 hour Holter recording)

For practical reasons or due to concerns that invasive or intensive tests would affect subsequent measurements (e.g., maximal exercise challenge can induce training effects), for the middle parts of the study (i.e., during the forced desynchrony) the following less invasive/ intensive identical test battery sessions were performed throughout each 20 h forced desynchrony:

• Core body temperature (CBT) for assessment of internal circadian phase

• Wrist actigraphy (and polysomnography is 4 participants) for estimation of sleep duration

• Hemodynamic, autonomic and endocrine responses to:

• Mental Stress (serial addition test for 10 minutes)

• Mild autonomic [postural) challenge (passive 60° head-up tilt for 15 minutes)

• Aerobic exercise challenge (bicycle exercise at 60% maximal heart rate for 15 minutes)

Additional measurements:

• Circadian Phase Assessment from core body temperature.

• Blood pressure and heart rate.

• Blood Sampling for autonomic, fibrinolytic and metabolic assays.

• Immune function: Astronauts experience various stressors that may result in inhibition of cell mediated immunity and increased reactivation of latent viruses [15,16]. Thus, comprehensive immune assessment was performed from whole blood samples collected with heparin at the beginning of study before either protocol, and twice during each of the short sleep and the long sleep protocols. Immune function was assessed by Dr. Brian E. Crucian and colleagues at NASA Johnson Space Center using standard techniques including peripheral leukocyte distribution by flow cytometry, T cell function, intracellular cytokine profiles, and secreted cytokine production profiles following T cell or monocyte stimulation [15]. In addition, innate reactivation of latent EBV (Epstein Barr Virus), HSV1 (herpes simplex virus 1), and VZV (Varicella Zoster Virus) was assessed from the DNA in liquid saliva samples taken at the beginning of study before either protocol, and every alternate day across both the short and long sleep protocols. These assays were performed by Dr. Satish K. Mehta and colleagues at NASA Johnson Space Center using real time polymerase chain reaction techniques [16].

• Rest/Activity cycles and Sleep (Actigraphy and Polysomnography): Verification of the rest/activity cycles imposed by the protocols and estimation of sleep was made throughout the entire study (baseline and in-laboratory phases) by wrist actigraphy worn on the non-dominant arm. In a subset of 4 participants, sleep was assessed on each study sleep opportunity during the laboratory phases by using polysomnography. Sleep data were visually scored according to standard criteria [13].

Statistical Comparisons: The main comparisons were between CV outcome measurements collected at baseline (Wake Periods 3 or 4 from each protocol) and after circadian disruption [with or without sleep loss] (Wake Periods 10 or 11 from each protocol). Differences across the long sleep protocol are attributed to a week of circadian disruption. Differences across the short sleep protocol relative to differences across the long sleep protocol are attributable to sleep loss. This sleep loss effect is seen as a significant statistical interaction between Condition [long sleep vs. short sleep] and Wake Period [beginning vs. end of protocol].

RESULTS

At time of this final report, no results have been published in peer-reviewed scientific journals, although updates were presented as posters at the NASA Human Research Program (HRP) Investigators’ Workshops in 2013 and 2014, and the main results were presented in an oral presentation at the HRP Investigators’ Workshop in 2015. It is anticipated that publications will appear in 2016 or 2017.

References

1. Zhu, H., H. Wang, and Z. Liu, Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review. Int J Occup Med Environ Health, 2015. 28(5): p. 793-802.

2. Rai, B., J. Kaur, and B.H. Foing, Stress, workload and physiology demand during extravehicular activity: a pilot study. N Am J Med Sci, 2012. 4(6): p. 266-9.

3. Thirsk, R., et al., The space-flight environment: the International Space Station and beyond. Cmaj, 2009. 180(12): p. 1216-20.

4. Copinschi, G., Metabolic and endocrine effects of sleep deprivation. Essent Psychopharmacol, 2005. 6(6): p. 341-7.

5. Scheer, F.A., et al., Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A, 2009. 106(11): p. 4453-8.

6. Leproult, R., U. Holmback, and E. Van Cauter, Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes, 2014. 63(6): p. 1860-9.

7. Hu, K., et al., Endogenous circadian rhythm in vasovagal response to head-up tilt. Circulation, 2011. 123(9): p. 961-70.

8. D'Aunno, D.S., et al., Effect of short- and long-duration spaceflight on QTc intervals in healthy astronauts. Am J Cardiol, 2003. 91(4): p. 494-7.

9. Mittleman, M.A., Air pollution, exercise, and cardiovascular risk. N Engl J Med, 2007. 357(11): p. 1147-9.

10. Reitz, C.J. and T.A. Martino, Disruption of Circadian Rhythms and Sleep on Critical Illness and the Impact on Cardiovascular Events. Curr Pharm Des, 2015. 21(24): p. 3505-11.

11. Myerburg, R.J., et al., A biological approach to sudden cardiac death: structure, function and cause. Am J Cardiol, 1989. 63(20): p. 1512-6.

12. Czeisler, C.A., et al., Stability, precision, and near-24-hour period of the human circadian pacemaker. Science, 1999. 284(5423): p. 2177-81.

13. Iber C, A.-I.S., Chesson AL Jr., Quan SF, The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. 1st ed. 2007, IL: Westchester.

14. Barger, L.K., et al., Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study. Lancet Neurol, 2014. 13(9): p. 904-12.

15 Crucian BE, Stowe RP, Pierson DL, Sams CF. Immune system dysregulation following short- vs long-duration spaceflight. Aviat Space Environ Med. 2008. 79: 835-43.

16 Mehta SK, Laudenslager ML, Stowe RP, Crucian BE, Sams CF, Pierson DL. Multiple latent viruses reactivate in astronauts during Space Shuttle missions. Brain Behav Immun. 2014;41: p. 210-7.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Rahman SA, Castanon-Cervantes O, Scheer FA, Shea SA, Czeisler CA, Davidson AJ, Lockley SW. "Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans." Brain Behav Immun. 2015 Jul;47:4-13. Epub 2014 Nov 13. http://dx.doi.org/10.1016/j.bbi.2014.11.003 ; PubMed PMID: 25452149; PubMed Central PMCID: PMC4430446 , Jul-2015
Articles in Peer-reviewed Journals Swanson CM, Shea SA, Stone KL, Cauley JA, Rosen CJ, Redline S, Karsenty G, Orwoll ES. "Obstructive sleep apnea and metabolic bone disease: insights into the relationship between bone and sleep." J Bone Miner Res. 2015 Feb;30(2):199-211. Review. https://doi.org/10.1002/jbmr.2446 ; PubMed PMID: 25639209; PubMed Central PMCID: PMC4572893 , Feb-2015
Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 09/30/2015  
Task Last Updated: 07/30/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham And Women's Hospital, Inc. 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Scheer, Frank  Ph.D. Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Matthew, Butler  Ph.D. Brigham and Women's Hospital, Inc. 
Barr, David  Ph.D. Brigham and Women's Hospital, Inc. 
Key Personnel Changes / Previous PI: July 2013: Since the last annual report, Matthew Butler, PhD has reduced effort and David Barr, PhD has assumed Dr. Butler's project leader duties.
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 9/30/2015, per PI and NSSC information (Ed., 8/5/14)

Task Description: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Under extremely physiologically challenging circumstances, i.e. microgravity, astronauts are expected to perform tasks that add additional physical and mental stress to their cardiovascular system such as space walks or robotic operations during EVAs. During space missions astronauts are exposed to unusual light-dark cycles (e.g. Martian day length: 24.65 hrs) that would be expected to cause circadian misalignment resulting in sleep disturbances, sleep loss, and poor quality sleep. In addition, almost all astronauts report chronic sleep curtailment due to mission requirements such as working ‘slam shifts’ before EVAs and extended shifts during EVAs. The sleeping conditions on the ISS, e.g. cramped crew quarters, noise, and heat, also add to the reported sleep curtailment. Data from laboratory and epidemiological studies have shown that chronic sleep curtailment and circadian misalignment changes endocrine, inflammatory, and cardiovascular function; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope, hypertension, diabetes, and metabolic syndrome. Moreover, adverse cardiac events show a clear day-night pattern, with a peak in the morning. In addition, it is well know than microgravity itself impacts cardiovascular functioning resulting in decreased circulating blood volume, decreased central venous blood pressure, increased stroke volume and increased cardiac output, potentially leading to cardiac rhythm disturbances that have been documented during spaceflight previously. To date we know little to nothing about the synergetic effects of chronic sleep restriction, circadian misalignment, and physical and mental stressors on cardiovascular functioning. The main goals of this NASA project are (1) to characterize the alterations (and potential maladaptations) of cardiovascular function (i.e. hemodynamic, autonomous nervous functioning, cardiac vulnerability) associated with chronic sleep restriction and circadian misalignment potentially occurring during space missions; (2) to characterize the effects of different types of stressors (postural, exercise, and mental stressors; except microgravity) on cardiovascular functioning; and (3) to identify the synergetic effects of chronic sleep restriction, circadian misalignment, and different stressors, potentially identifying vulnerable periods with an increased likelihood of adverse cardiac events during space missions. Our studies of sleep and circadian stressors on cardiovascular performance are relevant to astronauts in space flight as well as the many workers on Earth who experience similar conditions, albeit with gravity, during shift work.

Research Impact/Earth Benefits: Curtailed sleep and circadian disruptions are common features of modern life, on Earth as well as in space. Night-shift work is common among factory workers, police, fire fighters, and nurses, and such work has been identified as a risk factor for a host of diseases, including cardiovascular disease, stroke, and metabolic disorders. Our work therefore stands to impact health in astronauts, health in workers on earth, and may point to countermeasures and improvements in work-schedule design.

The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). This project specially aims to address gaps CV1 which asks “What are the in-flight alterations in cardiac structure and function?” and Gap CV8 which asks “Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?” Cardiac arrhythmias have been observed in astronauts and are considered a major risk endangering the success of space missions. In addition to myocardial structural changes, such arrhythmias can be triggered by numerous interacting and summating stressors (e.g., exercise, sleep loss, working during the biological night [‘circadian misalignment’]) causing changes in cardiovascular risk markers, such as increased blood pressure, cardiac vagal withdrawal, sympathetic activation, and promotion of hemostatic mechanisms. Current research in this focus area examines the clinical expression of cardiac atrophy by using in-flight Holter monitoring and ultrasound assessment of potentially long-term changes in cardiac structure and function with spaceflight (e.g., pre-flight, every 2-4 weeks during flight, and post-flight). Our current study complements these ongoing research activities by elucidating the effects on cardiovascular risk markers of two of the most debilitating aspects of space flight: circadian misalignment and chronic sleep loss. Moreover, to realistically simulate the stresses encountered by astronauts, we are assessing the synergistic effect of behavioral stressors together with the effects of circadian misalignment and prolonged sleep loss.

Our project has implications to Risk #27 - Risk of Performance Errors Due to Sleep Loss, Circadian Desynchronization, Fatigue, and Work Overload [Behavioral Health and Performance (BHP) Element of the HRP]. BHP focuses on the effects of sleep loss, fatigue, circadian misalignment and work overload on performance. Current countermeasures under investigation include recommendations concerning sleep hygiene, work-rest schedules, and optimal lighting requirements for the space vehicle, as well as safe and efficacious methods for implementing lighting as a countermeasure. Specifically, we share interest with the following identified gaps:

•Sleep 4 - How can individual astronauts’ vulnerabilities to sleep loss and circadian rhythms best be determined?; •Sleep 5 - How can light be used to optimally minimize circadian problems in space; •Sleep 8 - How are physical and cognitive workloads managed optimally in space relative to fatigue and recovery?

Knowledge about impaired cardiovascular function and periods of vulnerability for adverse cardiac events would contribute substantially to the above mentioned gaps and would enable knowledge integration between the Cardiovascular Alterations Team and the Human Factors and Performance Team.

Astronauts experience circadian misalignment, sleep loss, and different mental and physical stressors during missions; it is possible that these conditions contribute to sub-optimal cardiovascular function and that these effects will be exacerbated by stressors such as exercise during EVAs and postural stresses on return to Earth. Nevertheless, to date, we have little-to-no knowledge about how the relevant hemodynamic, autonomic, hemostatic, vascular, and endothelial biomarkers that comprise our dependent variables, react to simultaneous challenging circumstances of circadian misalignment, sleep loss and physical or mental exertion/stress. Once the effects of circadian misalignment, sleep loss, and different stressors are determined and vulnerable periods are identified, we hope to develop measures to alleviate or limit the risks by both ensuring proper circadian entrainment and sleep, and by ensuring activities that particularly challenge the cardiovascular system are avoided at specific vulnerable states of circadian misalignment and sleep loss. This could inform a new gap related to ‘inter-individual vulnerabilities’ to challenging work environments, including countermeasures and improvements of already existing challenging work environments (space flight and shift work), and better screening tools for future employees experiencing these work environments.

Finally, our previous work with healthy volunteers on Earth has shown that circadian disruption adversely affects metabolism and cardiovascular reactivity to stressors; two results with broad impact for society on Earth. The current project extends this work to consider the impact of short sleep, common across modern society, on how the circadian clock controls times of metabolic and cardiovascular vulnerability.

Task Progress & Bibliography Information FY2015 
Task Progress: We are studying healthy subjects throughout a within-subject design, with each subject undergoing two 11-day circadian misalignment protocols, achieved by advancing sleep periods by 4 hours every day (i.e., recurring 20 h ‘days’). One protocol provides adequate sleep (8.33 h of sleep opportunity per 20 h ‘day’; equivalent to 10 h of sleep opportunity per 24 h day) while the other protocol provides only 5 h of sleep opportunity per 20 h ‘day’ (equivalent to 6 h of sleep opportunity per 24 h day), thereby mimicking the average reported sleep duration of astronauts. In both protocols, subjects perform a stress battery each experimental ‘day’ while their responses to mental, exercise (bicycle), and postural (tilt-table) stresses are assessed. For each stressor we record baseline, stress-related, and recovery data. Cardiovascular function is assessed by markers of hemodynamic, hemostatic, autonomic, and vascular endothelial function. Using this approach, with subjects in conditions free of time cues, the effects of the stressors are being assessed at all phases of the internal biological clock. In addition to these variables obtained daily, all subjects participate in an intensive clinically relevant cardiovascular test battery before and after the sleep and circadian treatments. These include echocardiography to measure heart function and structure, brachial artery ultrasound to examine blood vessel function and stiffness, a maximum exercise test, and a longer postural stress to assess blood pressure regulation, including susceptibility to syncope.

Recruiting Report : To date we have received calls from 2148 people, of whom 125 were deemed eligible, available to participate, and were sufficiently interested to give their consent to start the screening procedures. Of these 125 subjects, 98 were found to be ineligible based on tests and/or examinations results and in a few cases because of a subject’s inability or unwillingness to liberate the many weeks of free time required for successful participation in the study. The remaining 27 subjects all gave informed consent for participation in the intensive research phase of the study. Prior to entry in the lab, 8 subjects either withdrew or were excluded from the study. Some of the reasons for withdrawal were non compliance to required sleep wake cycle, low fitness levels determined from maximal exercise test, loss of interest or changes in personal circumstances impacting ability to commit the time required for the in-laboratory stays in the hospital. We intended to study 16 subjects in the laboratory. We initiated in-patient studies in the remaining 19 participants, 14 have completed the protocol successfully, with only partial data sets from the remaining 5 participants who did not fully complete both of the 11-day in-lab studies.

Data Analysis and Results. This project covers one experiment with two randomized, single blind conditions. Thus, we cannot yet report un-blinded results until all group analyses have been performed. We are beginning data analysis of individuals and preparing for group analysis. We anticipate all group analyses, including un-blinding, will be completed by early 2015.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Barr DA, Butler MP, Rueger M, Myers S, Ollmann A, Smales C, Tzingantcheva AD, Crucian BE, Mehta SK, Pierson DL, Quiriarte H, Scheer FAJL, Shea SA. "BLINDED PRELIMINARY DATA: Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors commonly encountered during space missions." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. , Feb-2014

Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 09/30/2014  
Task Last Updated: 07/26/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham And Women's Hospital, Inc. 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Scheer, Frank  Ph.D. Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Matthew, Butler  Brigham and Women's Hospital, Inc. 
Key Personnel Changes / Previous PI: July 2013: Since the last annual report, Dr. Melanie Rueger has left the group. Dr. Matthew Butler has assumed project leader duties.
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Task Description: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Under extremely physiologically challenging circumstances, i.e. microgravity, astronauts are expected to perform tasks that add additional physical and mental stress to their cardiovascular system such as space walks or robotic operations during EVAs. To date we know little to nothing about the synergetic effects of chronic sleep restriction, circadian misalignment, and physical and mental stressors on cardiovascular functioning. The main goals of this four year NASA project are (1) to characterize the alterations (and potential maladaptations) of cardiovascular function (i.e. hemodynamic, autonomous nervous functioning, cardiac vulnerability) associated with chronic sleep restriction and circadian misalignment potentially occurring during space missions; (2) to characterize the effects of different types of stressors (postural, exercise, and mental stressors; except microgravity) on cardiovascular functioning; and (3) to identify the synergetic effects of chronic sleep restriction, circadian misalignment, and different stressors, potentially identifying in vulnerable periods with an increased likelihood of adverse cardiac events during space missions.

During space missions astronauts are exposed to unusual light-dark cycles (e.g. Martian day length: 24.65 hrs) that would be expected to cause circadian misalignment resulting in sleep disturbances, sleep loss, and poor quality sleep. In addition, almost all astronauts report chronic sleep curtailment due to mission requirements such as working ‘slam shifts’ before EVAs and extended shifts during EVAs. The sleeping conditions on the ISS, e.g. cramped crew quarters, noise, and heat, also add to the reported sleep curtailment. Data from laboratory and epidemiological studies have shown that chronic sleep curtailment and circadian misalignment changes endocrine, inflammatory, and cardiovascular function; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope, hypertension, diabetes, and metabolic syndrome. Moreover, adverse cardiac events show a clear day-night pattern, with a peak in the morning. In addition, it is well know than microgravity itself impacts cardiovascular functioning resulting in decreased circulating blood volume, decreased central venous blood pressure, increased stroke volume and increased cardiac output, potentially leading to cardiac rhythm disturbances that have been documented during spaceflight previously. Our studies of sleep and circadian stressors on cardiovascular performance are relevant to astronauts in space flight as well as the many workers on Earth who experience similar conditions, albeit with gravity, during shift work.

Research Impact/Earth Benefits: Curtailed sleep and circadian disruptions are common features of modern life, on Earth as well as in space. Shift workers include factory workers, police, fire fighters, and nurses, and such work has been identified as a risk factor for a host of diseases, including cardiovascular disease, strokes, and metabolic disorders. Our work therefore stands to impact health in astronauts, health in workers on Earth, and may point to countermeasures and improvements in work schedule design.

The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). This project specially aims to address gaps CV1 which asks “What are the in-flight alterations in cardiac structure and function?” and Gap CV8 which asks “Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted? Cardiac arrhythmias have been observed in astronauts and are considered a major risk endangering the success of space missions. In addition to structural changes, such arrhythmias can be triggered by numerous interacting and summating stressors (e.g., exercise, sleep deprivation, working during the biological night [‘circadian misalignment’]) causing changes in cardiovascular risk markers, such as increased blood pressure, cardiac vagal withdrawal, sympathetic activation, and promotion of hemostatic mechanisms. Current research in this focus area examines the clinical expression of cardiac atrophy by using in-flight Holter monitoring and ultrasound assessment of potentially long-term changes in cardiac structure and function with spaceflight (e.g., pre-flight, every 2-4 weeks during flight, and post-flight). Our current study complements these prior research activities by elucidating the effects on cardiovascular risk markers of two of the most debilitating aspects of space flight: circadian misalignment and chronic sleep loss. Moreover, to realistically simulate the stresses encountered by astronauts, we are assessing the synergistic effect of behavioral stressors together with the effects of circadian misalignment and prolonged sleep loss.

Our project has implications to Risk #27 - Risk of Performance Errors Due to Sleep Loss, Circadian Desynchronization, Fatigue, and Work Overload [Behavioral Health and Performance (BHP) Element of the HRP]. BHP focuses on the effects of sleep loss, fatigue, circadian misalignment and work overload on performance. Current countermeasures under investigation include recommendations concerning sleep hygiene, work-rest schedules, and optimal lighting requirements for the space vehicle, as well as safe and efficacious methods for implementing lighting as a countermeasure. Specifically, we share interest with the following identified gaps:

•Sleep 4 - How can individual astronauts’ vulnerabilities to sleep loss and circadian rhythms best be determined?; •Sleep 5 - How can light be used to optimally minimize circadian problems in space; •Sleep 8 - How are physical and cognitive workloads managed optimally in space relative to fatigue and recovery?

Knowledge about impaired cardiovascular function and periods of vulnerability for adverse cardiac events would contribute substantially to the above mentioned gaps and would enable knowledge integration between the Cardiovascular Alterations Team and the Human Factors and Performance team.

Astronauts experience circadian misalignment, sleep deprivation, and different mental and physical stressors during missions; it is possible that these conditions contribute to sub-optimal cardiovascular function and that these effects will be exacerbated by stressors such as exercise during EVAs and postural stresses on return to earth. Nevertheless, to date, we have little to no knowledge about how the relevant hemodynamic, autonomic, hemostatic, vascular, and endothelial biomarkers that comprise our dependent variables, react to challenging circumstances of circadian misalignment, sleep loss and physical or mental exertion/stress. Once the effects of circadian misalignment, sleep deprivation, and different stressors are determined and vulnerable periods are identified, we hope to develop measures to alleviate or limit the risks by both ensuring proper circadian entrainment and sleep, and by ensuring activities that particularly challenge the cardiovascular system are avoided at specific vulnerable states of circadian misalignment and sleep deprivation. This could inform a new gap related to ‘inter-individual vulnerabilities’ to challenging work environments, including countermeasures and improvements of already existing challenging work environments (space flight and shift work), and better screening tools for future employees experiencing these work environments.

Finally, our previous work with healthy volunteers on Earth has shows that circadian disruption adversely affects metabolism and cardiovascular reactivity to stressors; two results with broad impact for society on Earth. This project extends these work to consider the impact of short sleep, common across modern society, on how the circadian clock controls times of metabolic and cardiovascular vulnerability.

Task Progress & Bibliography Information FY2014 
Task Progress: 1. Introduction

The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Several factors impact cardiovascular functioning in space, including microgravity, sleep loss, sleeping or remaining awake at the ‘wrong’ times according to the internal body clock (circadian misalignment), physical, and mental stress. The project is assessing the contributions of reduced sleep, circadian misalignment, and varied physical and mental stresses on cardiovascular function, simulating many of the physiological stresses that occur throughout long missions.

This ground-based research will help to determine whether long-duration spaceflight (exclusive of radiation effects) leads to important changes in cardiovascular structure and function. This has been identified as an important concern for the Cardiac Alterations research area focusing on research and technology development to support crew health and performance in space explorations missions.

1.1. Specific aims

The specific aims of the protocol are to determine:

1. The effect of circadian misalignment on cardiovascular function. 2. The effect of chronic sleep loss on cardiovascular function. 3. The synergetic effects of circadian misalignment, chronic sleep loss, plus different stressors (postural, exercise, and mental stress) on cardiovascular function.

1.2. Background

In the past, we found that the internal circadian system modulates many important cardiovascular risk markers at rest, and that behavioral stressors have different effects when they occur at different times of day. For example, circulating adrenalin is high during the day and low at night, but additionally, the adrenalin response to exercise varies across the day, with peaks in exercise reactivity in the morning and evening. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events. We now wish to study the additional effect of sleep loss on these variables, better simulating the anticipated stresses of space flight.

1.3. Critical Path Roadmap questions addressed with this project

The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). This project specially aims to address gaps CV1 which asks “What are the in-flight alterations in cardiac structure and function?” and Gap CV8 which asks “Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted? Cardiac arrhythmias have been observed in astronauts and are considered a major risk endangering the success of space missions. To realistically simulate the stresses encountered by astronauts, we are assessing the synergistic effect of behavioral stressors together with the effects of circadian misalignment and prolonged sleep loss.

Our project also has implications to Risk #27 - Risk of Performance Errors Due to Sleep Loss, Circadian Desynchronization, Fatigue, and Work Overload [Behavioral Health and Performance (BHP) Element of the HRP]. BHP focuses on the effects of sleep loss, fatigue, circadian misalignment and work overload on performance. Current countermeasures under investigation include recommendations concerning sleep hygiene, work-rest schedules, and optimal lighting requirements for the space vehicle, as well as safe and efficacious methods for implementing lighting as a countermeasure. Specifically, we share interest with the following identified gaps:

• Sleep 4 - How can individual astronauts’ vulnerabilities to sleep loss and circadian rhythms best be determined?; • Sleep 5 - How can light be used to optimally minimize circadian problems in space; • Sleep 8 - How are physical and cognitive workloads managed optimally in space relative to fatigue and recovery?

Knowledge about impaired cardiovascular function and periods of vulnerability for adverse cardiac events would contribute substantially to the above mentioned gaps and would enable knowledge integration between the Cardiovascular Alterations Team and the Human Factors and Performance team.

1.4. Potential benefits to society (e.g. increased understanding of disease process, etc)

This project will help identify the synergistic contributions of sleep loss, circadian misalignment, and three different stressors on cardiovascular alterations, thereby simulating many of the physiological stresses that occur throughout long missions. Characterizing these effects on cardiovascular function may help us develop appropriate countermeasures to limit and/or alleviate adverse cardiovascular function during long and short duration space missions. Identifying vulnerable periods in which sleep loss, circadian misalignment, and different stressors lead to malfunctioning of the cardiovascular system may help us to improve work schedules and life-style interventions for shift workers as circadian misalignment and sleep deprivation are hallmarks of shift work.

2. Materials and Methods

Healthy non-obese participants, age 30-55, are being studied in a within-subject design, with each subject undergoing two 11-day circadian misalignment protocols, achieved by advancing sleep periods by 4 hours every day (i.e., recurring 20 h ‘days’). One protocol provides adequate sleep (equivalent to 10 h of sleep opportunity per 24 h day) while the other protocol restricts sleep (equivalent to 6 h of sleep opportunity per 24 h day), thereby mimicking the average reported sleep duration of astronauts. In both protocols, subjects perform a sequence of standardized stresses each experimental ‘day’ including mental, exercise (bicycle), and postural (tilt-table) stresses. For each stressor we record baseline, stress-related and recovery data. Cardiovascular function is assessed by markers of hemodynamic, hemostatic, autonomic and vascular endothelial function, for example with beat-to-beat blood pressure, EKG, and sampling of blood, urine, and saliva for hormone and biomarker analysis. Using this approach, with subjects in conditions free of time cues, the effects of the stressors are being assessed at all phases of the internal biological clock.

In addition to these variables, obtained daily, all subjects participate in an extensive clinically relevant cardiovascular function test battery before and after the sleep and circadian treatments. These include echocardiography to measure heart function and structure, brachial artery ultrasound to examine blood vessel function and stiffness, a maximum exercise test, and a longer postural stress to assess blood pressure regulation. Combining the day-by-day results and the longer changes over the course of the experiment will yield information about both the short-term and longer-term nature of these stressors. For example, an immediate time of day vulnerability may explain why heart attacks cluster in the morning, but a long term exposure to sleep loss and circadian disruption may exacerbate this vulnerability.

3. Results

This grant covers one experiment with two randomized, single blind conditions; the study is ongoing and results are blinded to reduce the risk of bias throughout the analysis phase. Thus, we cannot yet report unblinded results for our primary outcome variables. Secondary analyses performed by co-investigators at JSC in Houston, are ongoing and unblinded.

Recruiting Report and Subject Completion Timeline. Because of the extended in-lab commitment that participants must make, health screening is rigorous and attrition during the screening process due to ineligibility (physiological, medical, or psychological) and difficulty in committing the time is high. To date we have received calls from 1494 people, of whom 103 were deemed eligible, available to participate, and were sufficiently interested to give their consent to start the screening procedures. Of these 103 people, 19 subjects matched our criteria for study, and provided informed consent to participate. Of these 19, thirteen initiated the study, and ten completed both 11-day visits. Participant completion is therefore on schedule.

Immune Function. In collaboration with Dr. Crucian and Dr. Satish, at NASA’s JSC in Houston, immune function parameters have been investigated in blood samples taken during and after each circadian misalignment protocol. We found alterations in the bulk leukocyte subsets following the short sleep protocol, which were qualitatively similar to immune alterations observed during space flight. These results were presented at the NASA Human Research Program Investigators' Workshop (February 12–14, 2013, Galveston, Texas) and at the annual international SLEEP 2013 meeting in Baltimore, MD, 1-5 June 2013 (see below).

Other Assays. The plasma samples from all participants studied so far are currently being assayed together as a batch for markers of blood clotting (tPA, PAI-1) and autonomic function (epinephrine, and norephinephrine). Samples from the remaining six subjects will be assayed together as a second batch after completion of the remaining 6 participants.

Data Analysis Plans. We anticipate finishing data collection on all subjects during the winter/spring of 2014, after which full unblinded data analysis will commence.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Rueger M, Crucian B, Mehta SK, Pierson DL, Sams C, Scheer FA, Butler MP, Tzigantcheva AD, Smales C, Shea SA. "Effects of sleep deprivation and circadian misalignment on immunological markers in humans." SLEEP 2013--27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A101. Abstract 279. http://www.journalsleep.org/Resources/Documents/2013AbstractSupplement.pdf , Jun-2013

Abstracts for Journals and Proceedings Ruger M, Crucian B, Mehta SK, Pierson DL, Sams C, Scheer FAJL, Butler MP, Tzigantcheva AD, Smales C, Shea SA. "Preliminary results on the effects of sleep deprivation and circadian misalingment on immunological markers in habitually active particpants." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 09/30/2014  
Task Last Updated: 07/11/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham And Women's Hospital, Inc. 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Scheer, Frank  Ph.D. Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Rueger, Melanie  Ph.D. Brigham and Women's Hospital, Inc. 
Key Personnel Changes / Previous PI: Since the last annual report, the following staff members have left the group: Yusef Mohamed and Viqar Hussein (role: research assistant). The following staff members have been added to the study: Samantha Meyers and Adriana Tzelcheva (role: research assistants).
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Task Description: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Under extremely physiologically challenging circumstances, i.e. microgravity, astronauts are expected to perform tasks that add additional physical and mental stress to their cardiovascular system such as space walks or robotic operations during EVAs. To date we know little to nothing about the synergetic effects of chronic sleep restriction, circadian misalignment, and physical and mental stressors on cardiovascular functioning. The main goals of this four year NASA project are (1) to characterize the alterations (and potential maladaptations) of cardiovascular function (i.e. hemodynamic, autonomous nervous functioning, cardiac vulnerability) associated with chronic sleep restriction and circadian misalignment potentially occurring during space missions; (2) to characterize the effects of different types of stressors (postural, exercise, and mental stressors; except microgravity) on cardiovascular functioning; and (3) to identify the synergetic effects of chronic sleep restriction, circadian misalignment, and different stressors, potentially identifying in vulnerable periods with an increased likelihood of adverse cardiac events during space missions.

During space missions astronauts are exposed to unusual light-dark cycles (e.g. Martian day length: 24.65 hrs) that would be expected to cause circadian misalignment resulting in sleep disturbances, sleep loss, and poor quality sleep. In addition, almost all astronauts report chronic sleep curtailment due to mission requirements such as working ‘slam shifts’ before EVAs and extended shifts during EVAs. The sleeping conditions on the ISS, e.g. cramped crew quarters, noise, and heat, also add to the reported sleep curtailment. Data from laboratory and epidemiological studies have shown that chronic sleep curtailment and circadian misalignment changes endocrine, inflammatory, and cardiovascular function; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope, hypertension, diabetes, and metabolic syndrome. Moreover, adverse cardiac events show a clear day-night pattern, with a peak in the morning. In addition, it is well know than microgravity itself impacts cardiovascular functioning resulting in decreased circulating blood volume, decreased central venous blood pressure, increased stroke volume and increased cardiac output, potentially leading to cardiac rhythm disturbances that have been documented during spaceflight previously. With the anticipated return of humans to the moon in 2020 and the preparation for human explorations of Mars and other destinations in the solar system it becomes imperative to determine the cardiovascular risks for crew members on these missions, and develop countermeasures to limit or alleviate those risks.

Research Impact/Earth Benefits: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Several factors impact cardiovascular functioning in space, microgravity, sleep loss, physical and mental stress amongst them. The project will identify the independent contributions of sleep loss, circadian misalignment, and varied stressors on cardiovascular alterations, as well as their synergetic effects, thereby simulating many of the physiological stresses that occur throughout long missions. Characterizing these effects on hemodynamic and autonomic function may help us to develop appropriate countermeasures to limit and/or alleviate adverse cardiovascular function during long and short duration space missions.

Identifying vulnerable periods in which sleep deprivation, circadian misalignment, and different stressors lead to vulnerabilities of the cardiovascular system will also be beneficial to improving work schedules and life-style interventions for shift workers as circadian misalignment and sleep deprivation are hallmarks of shift work.

Task Progress & Bibliography Information FY2013 
Task Progress: After obtaining IRB approval and completion of staff training, to date we have actively recruited 73 subjects who gave their consent to start the screening procedures. 62 of these 73 subjects were found to be ineligible based on tests and/or examinations results and in a few cases because of a subject’s inability or unwillingness to liberate the many weeks of free time required for successful participation in the study. The remaining 11 subjects all gave informed consent for participation in the intensive research phase of the study.

Two of these 11 subjects were later excluded because the maximal oxygen consumption test prior to the laboratory stay revealed possible abnormalities in their EKGs. These subjects received their test results in report form and were advised to follow-up with their Primary Care Physicians. A third subject was excluded due to insufficient and inconsistent actigraphy data in the week leading up to the in-patient study. Losing these three subjects after they successfully completed all other screening procedures put us behind schedule in the first quarter of 2012 as we had all visits booked for the subjects and no back-ups could be immediately recruited to fill their places. Due to the nature of the study, i.e. two 11 day in-laboratory stays, at least 3 weeks apart, bookings for maximal oxygen consumption tests, brachial and cardiac ultrasound tests must be made a month in advance and subjects also rely on fixed dates for their planning and time commitment. Based on this experience we now try to ensure that we have a back-up ‘alternate’ subject that is at the same stage in the screening process and indicates flexibility to potentially fill the spot of a subject who drops out or is excluded based on screening test results.

We initiated in-patient studies in six of the remaining eight subjects. Of these, one subject withdrew from the study due to nausea and light-headedness during the tilt table test (this withdrawal was previously reported in the first annual report). Since the last progress report, a separate subject developed high blood pressure during the first in-laboratory stay and was withdrawn from the study as medical precaution. An adverse event report regarding this subject was filled to the NASA and Partners’ IRB and both institutions deemed that no changes to the protocol were necessary. The remaining four subjects successfully completed both 11-day in-laboratory stays and all other study requirements.

The last two consented subjects are on the schedule to complete their in-patient stays mid July and mid August and end of August and mid September, respectively. Thus, we anticipate that we will have completed 6 of the total of 16 subjects through the entire protocol by the end of the second year. Thus, we are slightly behind schedule. Our research group is comprised of research staff who work on numerous protocols simultaneously, and our group recently completed two other major protocols and will be working on only one additional project in the foreseeable future. This will enable us to focus much more effort on this current study. Thus, we are confident that we will be able to catch up to the expected enrollment rate within the next 12-18 months.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Ruger M, Scheer FAJL, Barger LK, Lockley SW, Wang W, Johnston SL 3rd, Crucian B, Shea SA. "STUDY DESIGN: Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions." Presented at the 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012.

2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. , Feb-2012

Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 09/30/2014  
Task Last Updated: 07/29/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham And Women's Hospital, Inc. 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Scheer, Frank  Ph.D. Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Rueger, Melanie  Brigham and Women's Hospital, Inc. 
Key Personnel Changes / Previous PI: We added Yusef Mohamed to the study staff (role: Research Assisant). We removed Jenny Marks from the study staff (role: Research Assistant). We added Melanie Rueger, Ph.D. as a Co-I.
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Task Description: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Under extremely physiologically challenging circumstances, i.e. microgravity, astronauts are expected to perform tasks that add additional physical and mental stress to their cardiovascular system such as space walks or robotic operations during EVAs. To date we know little to nothing about the synergetic effects of chronic sleep restriction, circadian misalignment, and physical and mental stressors on cardiovascular functioning. The main goals of this four year NASA project are (1) to characterize the alterations (and potential maladaptations) of cardiovascular function (i.e. hemodynamic, autonomous nervous functioning, cardiac vulnerability) associated with chronic sleep restriction and circadian misalignment potentially occurring during space missions; (2) to characterize the effects of different types of stressors (postural, exercise, and mental stressors; except microgravity) on cardiovascular functioning; and (3) to identify the synergetic effects of chronic sleep restriction, circadian misalignment, and different stressors, potentially identifying in vulnerable periods with an increased likelihood of adverse cardiac events during space missions.

During space missions astronauts are exposed to unusual light-dark cycles (e.g. Martian day length: 24.65 hrs) that would be expected to cause circadian misalignment resulting in sleep disturbances, sleep loss, and poor quality sleep. In addition, almost all astronauts report chronic sleep curtailment due to mission requirements such as working ‘slam shifts’ before EVAs and extended shifts during EVAs. The sleeping conditions on the ISS, e.g. cramped crew quarters, noise, and heat, also add to the reported sleep curtailment. Data from laboratory and epidemiological studies have shown that chronic sleep curtailment and circadian misalignment changes endocrine, inflammatory, and cardiovascular function; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope, hypertension, diabetes, and metabolic syndrome. Moreover, adverse cardiac events show a clear day-night pattern, with a peak in the morning. In addition, it is well know than microgravity itself impacts cardiovascular functioning resulting in decreased circulating blood volume, decreased central venous blood pressure, increased stroke volume and increased cardiac output, potentially leading to cardiac rhythm disturbances that have been documented during spaceflight previously. With the anticipated return of humans to the moon in 2020 and the preparation for human explorations of Mars and other destinations in the solar system it becomes imperative to determine the cardiovascular risks for crew members on these missions, and develop countermeasures to limit or alleviate those risks.

Research Impact/Earth Benefits: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Several factors impact cardiovascular functioning in space, microgravity, sleep loss, physical and mental stress amongst them. The project will identify the independent contributions of sleep loss, circadian misalignment, and varied stressors on cardiovascular alterations, as well as their synergetic effects, thereby simulating many of the physiological stresses that occur throughout long missions. Characterizing these effects on hemodynamic and autonomic function may help us to develop appropriate countermeasures to limit and/or alleviate adverse cardiovascular function during long and short duration space missions.

Identifying vulnerable periods in which sleep deprivation, circadian misalignment, and different stressors lead to vulnerabilities of the cardiovascular system will also be beneficial to improving work schedules and life-style interventions for shift workers as circadian misalignment and sleep deprivation are hallmarks of shift work.

Task Progress & Bibliography Information FY2012 
Task Progress: To date there are no group results to report. After obtaining IRB approval in August 2011 we have trained our staff intensively on the procedures and techniques we are employing to collect the cardiovascular measures, i.e. the 60 and 80 degrees tilt tables test, 12-lead Holter Monitor, 3-led ECG, Portapress. Intensive training will ensure that these sensitive physiological measurements are carried out in a standardized fashion and with as little as possible inter-individual variability as possible. After completion of staff training, we started recruiting subjects and a total of 23 subjects so far have given their consent to start the screening process. Of those 23, 18 subjects were found ineligible based on test and/or examination results. Of the remaining five, three subjects gave informed research consent to enroll in the inpatient part of the protocol. Starting in the first quarter of 2011, we initiated inpatient studies in two of those three subjects, of which one subject withdrew from the study on day 4 of the inpatient protocol due to experiencing side effects (nausea and light-headedness) during the tilt table test. The second subject is currently completing his second inpatient stay and the third subject is scheduled to admit to the lab at the end of August 2011. There are two more subjects currently screening for the study. It is our goal to complete a total of 6 subjects by the end of this calendar year.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
 None in FY 2012
Project Title:  Identification of cardiometabolic vulnerabilities caused by effects of synergistic stressors that are commonly encountered during space missions Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2010  
End Date: 09/30/2014  
Task Last Updated: 09/20/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Shea, Steven  Ph.D. / Brigham And Women's Hospital, Inc./Harvard Medical School 
Address:  Sleep Disorders Research Program 
221 Longwood Ave, 036 BLI 
Boston , MA 02115-5804 
Email: sheast@ohsu.edu 
Phone: 503 494 2517  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham And Women's Hospital, Inc./Harvard Medical School 
Joint Agency:  
Comments: NOTE: PI currently at Oregon Health & Science University as of June 2016. 
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham And Women's Hospital, Inc. 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Scheer, Frank  Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Project Information: Grant/Contract No. NNX10AR10G 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NNX10AR10G 
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) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Bmed:Risk of Adverse Behavioral Conditions and Psychiatric Disorders
(3) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) BMed03:We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions (IRP Rev F)
(2) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(3) IM03:We have not defined and validated a terrestrial human analog for spaceflight-associated immune system dysregulation (IRP Rev E)
(4) IM08:We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight (IRP Rev E)
Task Description: The risk of adverse cardiac events has been listed as Priority 1 in the NASA Bioastronautics Roadmap (Risk Areas 5 and 6; 2005; http://bioastroroadmap.nasa.gov ). Under extremely physiological challenging circumstances, i.e. microgravity, astronauts are expected to perform tasks that add additional physical and mental stress to their cardiovascular system such as space walks or robotic operations during EVAs. To date we know little to nothing about the synergetic effects of chronic sleep restriction, circadian misalignment, and physical and mental stressors on cardiovascular functioning. The main goals of this four year NASA project are (1) to characterize the alterations (and potential maladaptations) of cardiovascular and cardiometabolic function (i.e. hemodynamic, haemostatic, autonomous nervous functioning, cardiac vulnerability, energy metabolism) associated with chronic sleep restriction and circadian misalignment occurring during short and long term duration space missions (e.g. Lunar sorti, Lunar outpost, and mission to Mars); (2) to characterize the effects of different types of stressors (postural, exercise, and mental stressors; except microgravity) on cardiovascular and cardiometabolic functioning during short and long term duration space missions; and (3) to identify the synergetic effects of chronic sleep restriction, circadian misalignment, and different stressors, potentially identifying in vulnerable periods with an increased likelihood of adverse cardiac events during short and long term duration space missions.

During space missions astronauts are exposed to unusual light-dark cycles (e.g. Martian day length: 24.65 hrs) that leads to circadian misalignment resulting in sleep disturbances, sleep loss, and poor quality sleep. In addition, almost all astronauts report chronic sleep curtailment due to mission requirements such as working ¿slam shifts¿ before EVAs and extended shifts during EVAs. The sleeping conditions on the shuttle or the ISS, e.g. cramped crew quarters, noise, and heat, also add to the reported sleep curtailment. Data from laboratory and epidemiological studies have shown that chronic sleep curtailment and circadian misalignment changes endocrine, inflammatory, and cardiovascular function; changes that potentially result in adverse health events, including cardiac arrhythmias, myocardial and peripheral vascular dysfunction, risk of syncope, hypertension, diabetes, and metabolic syndrome. Moreover, adverse cardiac events show a clear day-night pattern, with a peak in the morning. In addition, it is well know than microgravity itself impacts cardiovascular functioning resulting in decreased circulating blood volume, decreased central venous blood pressure, increased stroke volume and increased cardiac output, potentially leading to cardiac rhythm disturbances that have been documented during spaceflight previously.

With the anticipated return of humans to the moon in 2020 and the preparation for human explorations of Mars and other destinations in the solar system it becomes imperative to determine the cardiovascular risks for crew members on these missions, and develop countermeasures to limit or alleviate those risks.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2011 
Task Progress: New project for FY2011.

Bibliography Type: Description: (Last Updated: 08/14/2018) 

Show Cumulative Bibliography Listing
 
 None in FY 2011