Steinberg, Susan

NASA Technical Reports Server

 
2014 Cardiovascular Risks Standing Review Panel  
 
Status Review for: 
The Risk of Cardiac Rhythm Problems and  
The Risk of Orthostatic Intolerance During Re-Exposure to Gravity 
 
Final Report  
 
 
I.   Executive Summary and Overall Evaluation 
 
The 2014 Cardiovascular Risks Standing Review Panel (from here on referred to as the SRP) 
met for a site visit in Houston, TX on December 17-18, 2014.  The SRP received status updates 
on the Risk of Cardiac Rhythm Problems (Arrhythmia Risk) and the Risk of Orthostatic 
Intolerance during Re-Exposure to Gravity (OI Risk). 
 
The cardiovascular discipline lead, Dr. Michael Stenger, provided a thorough overview of 
progress within the past year.  Based on the scientific findings shared with the SRP, it appears as 
though additional knowledge is needed regarding the short- and long-term effects of spaceflight 
on the development of cardiac rhythm problems.  The SRP was unable to review the most recent 
International Space Station (ISS) data relevant to cardiac arrhythmias, which will be released 
after the conclusion of the 2014 meeting.  There appears to be sufficient scientific rationale to 
continue studying cardiac rhythm questions under the broader risk of cardiovascular disease. 
 
II. Comments Regarding the Risk of Cardiac Rhythm Problems 
(Arrhythmia) Status Review 
 
1.  Do the non-Arrhythmia gaps and tasks in the current research plan address valid 
questions that still need to be answered regardless of what risk they are mapped to in 
the future? 
 
Yes, the SRP found that the non-Arrhythmia gaps and tasks in the current research plan 
address valid questions that still need to be answered regardless of what risk they are 
mapped to in the future. 
 
2. Are we missing anything regarding the research content for the cardiovascular system? 
 
1) Arrhythmia 
The SRP does not believe that there was sufficient evidence presented during the 2014 
meeting to conclude that arrhythmia was a very low risk.  Significant study data 
regarding the risk of cardiac arrhythmias was not yet available for presentation.  More 
importantly, cardiac arrhythmias by their nature present at unpredictable times, but can 
have devastating consequences.  Furthermore, while improved screening for arrhythmia 
risk factors may reduce the risk of cardiac arrhythmias, the risk of clinically significant 
arrhythmias is not zero (Myerburg et al. Circulation 19981) and appropriate 
countermeasures such as an electrocardiogram (ECG) monitor, defibrillator and crew 
training need not be overly burdensome.  Of note, a one pound monitor/defibrillator is 
currently commercially available. 
 
https://ntrs.nasa.gov/search.jsp?R=20150008163 2019-08-31T10:46:10+00:00Z
  
 
2014 Cardiovascular Risks SRP Final Report 2 
 
During the 2014 meeting, several of the presented studies for the Arrhythmia Risk seem 
to suggest that a broader emphasis on spaceflight and cardiovascular disease risks may 
be warranted.  Notably, terrestrial research shows significant long-term cardiovascular 
risk associated with radiation (Finch et al. Rev Cardiovasc Med. 20142), stress (Steptoe 
et al. Nat Rev Cardiol. 20123), noise (Eriksson et al. Environ Health Perspect. 20144), 
and sleep disturbance (Westerlund et al. Eur J Epidemiol. 20135) – expected 
environmental conditions during long-duration spaceflight.  The SRP was briefed on 
several ongoing studies that address short- and long-term cardiovascular consequences 
of spaceflight.  Of particular interest, the Cardio Ox study will provide longitudinal data 
for up to five years post-spaceflight on several key cardiovascular parameters.  Since 
stress, endothelial damage and sleep disturbance are associated with increased blood 
pressure; 24-hour blood pressure measurement may provide valuable data after 
spaceflight. 
 
Broadening the scope of the risk to include additional aspects of cardiovascular disease 
is strongly recommended.  Areas of integration with other disciplines would fall under 
this broader cardiovascular risk, including the effects of space radiation on the 
development of cardiovascular disease or acceleration of existing subclinical 
cardiovascular disease and effects of behavioral aspects such as isolation on 
cardiovascular variables. 
 
2) Exercise and Ocular Injury 
During the 2014 meeting, the SRP was presented data that suggest spaceflight can lead 
to volume redistribution toward the eyes and visual alterations.  One of the current U.S. 
countermeasures includes resistance training (RT) using the Advanced Resistive 
Exercise Device (ARED).  While this countermeasure appears to be successful in 
counteracting bone loss and muscle atrophy, there were questions as to whether venous 
and intraocular pressure changes associated with exercise might be contributing to 
some of the visual alterations.  Interestingly, it was anecdotally noted that while the 
U.S. program emphasizes both RT and aerobic training (AT), the Russians tend to 
focus more on the AT (with some RT component primarily through bands).  It was also 
noted that the Russians deny any ocular issues, but that this is controversial, given that 
more recently the Russians have become engaged in the visual testing on the ISS.  The 
SRP recommends some consideration of integrative work between the cardiovascular 
discipline and Bone/Muscle disciplines on this potential concern.  It might be useful to 
look historically at prior space missions that did not have RT countermeasures and 
determine if visual alterations were reported.  It also seems appropriate to determine 
what type of arterial, venous and intraocular pressures are being generated during RT in 
microgravity and during head-down tilt, given the fluid redistribution in space.  While 
AT decreases intraocular pressure, RT can have a variable influence on pressure within 
the eye, largely depending on breathing patterns (Risner et al. J Glaucoma. 20096).  
Venous pressure and middle cerebral artery blood flow during RT are largely 
dependent on breathing patterns, and can change greatly during the Valsalva maneuver 
(Pott et al. J App. Physiology. April 20037).  It is possible that simple countermeasures 
such as proper breathing patterns during RT might diminish the increased venous 
pressure associated with RT. 
  
 
2014 Cardiovascular Risks SRP Final Report 3 
 
 
3. General Comments 
 
Integration Studies 
The SRP was asked during the 2014 meeting to address whether crossover studies 
among disciplines might be beneficial.  There was abundant evidence that HRP groups 
already cooperate effectively and appear to work collegially toward common goals.  A 
novel format that included presentations across disciplines and free time for discussion 
between groups led to a number of suggestions for crossover studies that could provide 
useful information. 
 
The SRP discussed the importance of integrating cardiovascular assessment into some 
of the isolation studies being considered by the behavioral group.  Isolation, depression, 
and psychological stress are risk factors for cardiovascular disease (Steptoe et al. Nat 
Rev Cardiol. 20123).  A three-year Mars mission would be associated with such risk 
factors, and it is important to consider what impact this might have on long-term 
cardiovascular health of these astronauts.  Moreover, the concept of 
isolation/depression/stress on cardiovascular health is of interest to the broader 
community, and potential interagency announcements with the National Institutes of 
Health (specifically the National Heart, Lung, and Blood Institute or the National 
Institute on Aging) might be considered.  The Antarctic isolation studies used to 
investigate behavioral responses to stress might also be used to measure cardiovascular 
changes in intima-media thickness, vascular biomarkers and blood pressure. 
 
Radiation exposure raises the risk of cancer, but may also accelerate vascular pathology 
(Finch et al. Rev Cardiovasc Med. 20142).  Measurement of endothelial function, 
vascular biomarkers, vascular rigidity and intima-media thickness in experimental 
models used to study the incidence of cancers might inform whether there is an 
increased cardiovascular risk during long-duration space missions. 
 
III. Comments regarding the Risk of Orthostatic Intolerance (OI) during 
Re-Exposure to Gravity Status Review 
 
1. Are we missing anything regarding the research content for the cardiovascular system? 
 
OI and Partial Gravity 
Dr. Stenger’s presentation of the progress made in the last year toward completion of 
the OI risk was greatly appreciated. This area is quite mature in terms of the amount of 
knowledge and development of countermeasures.  The focus of the prior year has 
largely been to continue data collection of cardiovascular responses to orthostatic 
challenges pre- and post-flight and to test the efficacy of the gradient compression 
garment to prevent OI.  To date, the focus has been on cardiovascular issues upon 
return to Earth.  With the future goal of a Mars mission, however, it is not clear if OI is 
a significant risk when landing in partial gravity.  Knowledge in this area is important, 
as there will be no medical support and no intravenous fluid administration post-
landing in this environment.  It is not clear if the gradient compression garment 
  
 
2014 Cardiovascular Risks SRP Final Report 4 
 
currently being tested for return to Earth will be optimal for partial gravity. 
 
Emotional Stress and OI 
The Functional Task Test (FTT), which examines OI risk during 1) sit-to-stand, 2) 
recovery from fall-to-stand test, and 3) walk test, are likely to yield very important 
information towards the progress of this risk.  However, the impact of emotional/mental 
stress on post-flight OI may be as important as physical stress.  When long-duration 
spaceflight astronauts returned to Earth, most had OI and most had sympathetic nervous 
activation, which would serve to temper their OI.  However, one astronaut failed to 
activate his sympathetic nerves, as is seen in some vaso-vagal faints (Meck et al. 
Psychosom Med. 20018).  In addition, findings of low vascular resistance in some 
returning astronauts with OI suggest ineffective sympathetic nervous activation and are 
characteristic of emotional faints (Waters et al. J Appl Physiol (1985). 20029).  Physical 
stressors such as cold and exercise usually activate the sympathetic nerves, are 
characterized by high blood norepinephrine levels and an increase in blood pressure.  
Psychological stressors are often accompanied by high blood epinephrine levels, 
vasodilation and sometimes by fainting (Evans et al. Auton Neurosci. 200110).  The 
compression garments seem to be quite successful for Earth re-entry where the post-
flight tests are standard and controlled, but difficulty during re-entry to gravity would 
be accompanied by mental stress.  The SRP suggests consideration of some emotional 
stressor during the FTT to determine blood pressure and heart rate changes.  Integration 
with the behavioral group on these tests seems logical, and ground-based analogs seem 
appropriate. 
 
IV. References 
 
1) Myerburg RJ, Mitrani R, Interian A, Jr., Castellanos A. Interpretation of outcomes of 
antiarrhythmic clinical trials: Design features and population impact. Circulation. 
1998;97:1514-1521. 
 
2) Finch W, Shamsa K, Lee MS. Cardiovascular complications of radiation exposure. Rev 
Cardiovasc Med. 2014;15:232-244. 
 
3) Steptoe A, Kivimaki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012; 9:360-
370. 
 
4) Eriksson C, Hilding A, Pyko A, Bluhm G, Pershagen G, Ostenson CG. Long-term 
aircraft noise exposure and body mass index, waist circumference, and type 2 diabetes: A 
prospective study. Environ Health Perspect. 2014;122:687-694. 
 
5) Westerlund A, Bellocco R, Sundstrom J, Adami HO, Akerstedt T, Trolle Lagerros Y. 
Sleep characteristics and cardiovascular events in a large swedish cohort. Eur J 
Epidemiol. 2013;28:463-473. 
 
6) Risner D, Ehrlich R, Kheradiya NS, Siesky B, McCranor L, Harris A. Effects of  exercise 
on intraocular pressure and ocular blood flow: a review. J Glaucoma. 2009 
  
 
2014 Cardiovascular Risks SRP Final Report 5 
 
Aug;18(6):429-36. 
 
7) Pott F, Van Lieshout JJ, Ide K, Madsen P, Secher NH: Middle cerebral artery blood 
velocity during intense static exercise is dominated by a Valsalva maneuver. J App. 
Physiology 1 April 2003 Vol. 94 no. 4,335-1344. 
 
8) Meck JV, Reyes CJ, Perez SA, Goldberger AL, Ziegler MG. Marked exacerbation of 
orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts. 
Psychosom Med. 2001 Nov-Dec;63 (6):865-73. 
 
9) Waters WW, Ziegler MG, Meck JV. Postspaceflight orthostatic hypotension occurs 
mostly in women and is predicted by low vascular resistance. J Appl Physiol (1985). 
2002 Feb; 92 (2): 586-94. 
 
10) Evans JM, Leonelli FM, Ziegler MG, McIntosh CM, Patwardhan AR, Ertl AC, Kim CS, 
Knapp CF Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men 
and women. Auton Neurosci. 2001 Oct 8;93(1-2):79-90. 
 
  
 
2014 Cardiovascular Risks SRP Final Report 6 
 
V. 2014 Cardiovascular Risks SRP Status Review:  Statement of Task for 
the Risk of Cardiac Rhythm Problems and the Risk of Orthostatic 
Intolerance during Re-Exposure to Gravity 
 
The 2014 Cardiovascular Risks Standing Review Panel (SRP) will participate in a Status Review that 
will occur via a site visit with the Human Research Program (HRP) Chief Scientist or Deputy Chief 
Scientist and members of the Human Health Countermeasures (HHC) Element.  The purpose of this 
review is for the SRP to:  
 
1. Receive an update by the HRP Chief Scientist or Deputy Chief Scientist on the status of 
NASA’s current and future exploration plans and the impact these will have on the HRP. 
 
2. Receive an update on any changes within the HRP since the 2013 SRP meeting. 
 
3. Receive an update by the Element or Project Scientist(s) on progress since the 2013 SRP 
meeting. 
 
a. The Risk of Cardiac Rhythm Problems  
The Arrhythmia risk is currently under review for retirement.  Since the Arrhythmia 
risk was created it has become a place to bookkeep other cardiovascular research 
related to fluid shifts or subclinical cardiovascular disease, both resulting from 
exposure to the spaceflight environment.  NASA is currently considering the creation 
of a new risk to address cardiovascular disease in spaceflight OR book keeping the 
non-Arrhythmia cardiovascular related research in other HRP risks.  Therefore, the 
2014 Cardiovascular Risks SRP is not being asked to conduct a Full Research Plan 
Review of the Arrhythmia risk, but is being asked to address the following two 
points: 
i. Do the non-Arrhythmia gaps and tasks in the current research plan address 
valid questions that still need to be answered regardless of what risk they are 
mapped to in the future? 
ii. Are we missing anything regarding the research content for the 
cardiovascular system? 
b. The Risk of Orthostatic Intolerance During Re-Exposure to Gravity  
Receive an update on the Orthostatic Intolerance risk since the 2013 SRP meeting. 
 
4. Participate in a discussion with the HRP Chief Scientist, Deputy Chief Scientist, and the 
Element regarding possible topics to be addressed at the next SRP meeting 
 
The 2014 Cardiovascular Risks SRP will produce a report/comments (specifically addressing #3a 
above) from this status review within 30 days of the 2014 update.  These comments will be submitted 
to the HRP Chief Scientist and copies will be provided to the HHC Element that sponsors the 
cardiovascular discipline and also made available to the other HRP Elements. The 2014 SRP Final 
Report will be made available on the Human Research Roadmap public website 
(http://humanresearchroadmap.nasa.gov/). 
 
 
  
 
2014 Cardiovascular Risks SRP Final Report 7 
 
VI. 2014 Cardiovascular Risks SRP Roster 
 
Panel Chair: 
Michael Ziegler, M.D. 
UCSD Medical Center 
200 West Arbor Drive 
San Diego, CA 92103 
Ph: 619-543-2885 
Email: mziegler@ucsd.edu 
 
Panel Members: 
Jason Carter, Ph.D.  
Michigan Technological University  
Department of Kinesiology and Integrative Physiology 
1400 Townsend Drive 
Houghton, MI 49931 
Ph: 906-487-2715 
Email: jcarter@mtu.edu   
 
Victoria Claydon, Ph.D. 
Simon Fraser University 
Department of Biomedical Physiology and Kinesiology 
8888 University Drive 
Burnaby, British Columbia, V5A 1S6 
Canada 
Ph: 778-782-8513 
Email: victoria_claydon@sfu.ca  
 
David Krummen, M.D. 
VA San Diego Medical Center/UCSD  
Sulpizio Cardiovascular Center  
14168 Half Moon Bay Drive 
Del Mar, CA 92014 
Ph: 858-922-9275 
Email: dkrummen@ucsd.edu   
 
Gail Thomas, Ph.D. 
Penn State Heart and Vascular Institute 
Penn State College of Medicine 
500 University Drive 
Hershey, PA 17033 
Ph: 717-531-0003, ext. 287087# 
Email: gthomas4@hmc.psu.edu 
 
 


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