Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers

Bungo, Michael W.

Hamilton, Douglas R.

Johnston, Smith L.

Levine, Benjamin D.

Platts, Steven H.

NASA Technical Reports Server

 Acronym: Integrated Cardiovascular 
 
Title: Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional 
Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias 
 
Principal Investigator(s):   
Benjamin D. Levine, M.D., Institute for Exercise and Environmental Medicine, Presbyterian Hospital and 
University of Texas Southwestern Medical Center at Dallas, Dallas, TX 
Michael W. Bungo, M.D., University of Texas Medical School, Houston, TX 
 
Co-Investigator(s):   
Steven H. Platts, Ph.D. Johnson Space Center, Houston, TX 
Douglas R. Hamilton, M.D., Ph.D., Wyle Laboratories, Houston, TX 
Smith L. Johnston, M.D., Johnson, Space Center, Houston, TX 
 
Contact(s):  
PI - Benjamin D. Levine, BenjaminLevine@TexasHealth.org, (214) 345-4620  
PI - Michael W. Bungo, Michael.W.Bungo@uth.tmc.edu, (713) 500-5532 
Primary - John Love, john.e.love@nasa.gov, (281) 483-7713 
Secondary - Cathy Modica, catherine.g.modica@lmco.com, (281) 218-3303 
 
Mailing Address:  
Dr. Benjamin D. Levine 
Institute for Exercise and Environmental Medicine  
Presbyterian Hospital of Dallas  
University of Texas – Southwestern  
7232 Greenville Ave., Ste. 435 
Dallas, TX  75231 
 
Dr. Michael W. Bungo 
University of Texas Medical School 
6431 Fannin St., MSB #1.242 
Houston, TX  77030 
 
Developer(s): Johnson Space Center, Human Research Program, Houston, TX 
 
Sponsoring Agency:  National Aeronautics and Space Administration (NASA) 
  
Increment(s) Assigned: 19, 20 
 
Mission Assigned: N/A 
 
Brief Research Summary (PAO): Cardiac Atrophy and Diastolic Dysfunction During and After Long 
Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk 
for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flight-
associated cardiac atrophy (deterioration) on the International Space Station crewmembers.   
 
Research Summary:  
 
• Atrophy (a decrease) in the size of the heart muscle appears to develop during space flight and 
its ground-based analogues (i.e., bedrest) which could lead to impaired functioning of the heart 
and low blood pressure or fainting upon return to gravity on the Earth, the moon or Mars. 
 
• Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight:  
Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac 
Arrhythmias (Integrated Cardiovascular) will determine how much cardiac atrophy occurs during 
https://ntrs.nasa.gov/search.jsp?R=20090014822 2019-08-30T06:35:55+00:00Z
 space flight, how fast and, whether this atrophy causes problems with the heart’s pumping or 
electrical function, and how both the atrophy and any associated changes develop. 
 
• The effects of this atrophy on how the heart fills, how blood pressure responds to the lack of and 
reintroduction to gravity (Earth, the moon and Mars), a crewmember’s ability to exercise, and the 
likelihood of developing unusual heart rhythms will also be determined, both in space on the 
International Space Station, and following return to Earth. 
 
• Results from this investigation will ensure crew health on future long-duration exploration 
missions and will help in the development of any needed countermeasures for the effects of 
space flight on the cardiovascular system. 
 
Detailed Research Description: Cardiac atrophy (decrease) appears to develop during space flight or 
its ground-based analogues, i.e., bedrest, leading to diastolic dysfunction (abnormal left ventricle in the 
heart)  and orthostatic hypotension, a condition where the blood pressure drops when an individual 
stands up. Such atrophy also may be a potential mechanism for the cardiac arrhythmias (irregular 
heartbeat) recently identified in some crewmembers after long-duration exposure to microgravity aboard 
the Mir space station. Recent studies has suggested that cardiac atrophy may be progressive, without a 
clear plateau over at least 12 weeks of bedrest, and thus may be a significant limiting factor for extended 
duration space exploration missions. Cardiac Atrophy and Diastolic Dysfunction During and After Long 
Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk 
for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent, time course and clinical 
significance of cardiac atrophy and identify its mechanisms. The functional consequences of this atrophy 
also will be determined for cardiac filling dynamics, orthostatic tolerance at gravity on Earth and fractional 
gravity (Mars and the moon) conditions, exercise tolerance, and arrhythmia susceptibility, both in space 
on the International Space Station (ISS), and following return to Earth. 
Integrated Cardiovascular will determine the magnitude of the left and right ventricular atrophy associated 
with long-duration space flight (using magnetic resonance imaging,MRI) and relate this atrophy to 
measures of physical activity and cardiac work inflight, determine the time course and pattern of the 
progression of cardiac atrophy inflight using cardiac ultrasound, determine the functional importance of 
cardiac atrophy for cardiac diastolic function and the regulation of stroke volume (volume of blood 
pumped by the right/left ventricle of the heart in one contraction) during gravitational transitions, and 
identify changes in ventricular conduction, depolarization and repolarization during and after long-duration 
space flight and relate these to changes in heart mass and morphology (shape and form). 
Project Type:  Payload 
 
Images and Captions:  
 
 Computer generated diagram of the Integrated Cardiovascular investigation onboard the ISS. Image 
courtesy of the Johnson Space Center, Human Research Program. 
 
Operations Location:  ISS Inflight 
 
Brief Research Operations:  
 
• Inflight operations include: 
• Resting echocardiograms (ECG), using the HRF Ultrasound, are performed four times during 
flight. An exercise ECG is performed before and after exercise one time during the expedition.  
• An ambulatory blood pressure, holter, activity monitoring occurs for 24-hours either before or after 
each resting and exercise ECG session. The data is downloaded and downlinked from all 
hardware to the HRF personal computer (PC) following the completion of each set of ECG  
sessions. 
• Logging of inflight exercise and medication will be obtained through data sharingwith other 
activities.  
 
• Preflight and postflight operations include: 
• Resting ECG before and after flight. An exercise ECG will occur once before and twice after flight. 
• An ambulatory blood pressure, holter, activity monitoring occurs for 48-hours two times before 
and one time (for 24 hours) after flight. A cardiac MRI, with magnetic resonance spectroscopy 
and gadolinium enhancement) once before and twice after flight are also required. 
• Graded tilt test with ECG once before and once after flight; exercise and medication logs will be 
obtained via data sharing. 
 
Operational Requirements:  A total of twelve subjects are required for this investigation.  Inflight 
scanning sessions are planned on flight day 14 (FD14) +/- 4-days, FD30 +/-5 days, FD75 +/-5 days, 
FD135 +/-5 days, and R-15 +/-4 days.  Ambulatory blood pressure, holter, activity monitoring is required 
within one week (preferably three days) of each session.  The total number of sessions required is 
dependent on mission length.  Both an operator and a subject are required for the ultrasound scans along 
with real-time video downlink to enable remote guidance by ground experts. 
Operational Protocols:  Inflight, resting ECG, using the HRF Ultrasound will be performed on FD14, 
FD30, FD135, and return plus 15-days (R+15) using real-time remote guidance.  On FD75, an exercise 
ECG session will be performed with measurements taken before and after exercise. Both the resting and 
exercise sessions will be preceded or followed by 24-hours of ambulatory blood pressure, holter, activity 
monitoring.  For these sessions, subjects will apply electrodes and then don the HRF Holter Monitor, ESA 
Cardiopres, and two Actiwatches (one at the waist and one at the ankle).  These devices will be worn for 
24-hours after which the devices will be doffed and the data from all experiment hardware will be 
downloaded to the HRF PC and downlinked to the ground.  Inflight exercise and medication logs will be 
obtained through data sharing.  
On the ground, resting ECG will be obtained between launch minus 21-days (L-21) and L-7 and again at 
return plus 7-days (R+7).  Exercise ECG will be performed between L-75 and L-60 and again at R+4 and 
R+14.  Preflight, ambulatory blood pressure,holter, activity monitoring for 48-hours will be conducted 
between L-75 and L-60 and again between L-21 and L-7.   
Postflight, ambulatory blood pressure, holter, activity monitoring for 24-hours will be conducted on R+0.  
Cardiac MRI (with Magnetic Resonance Spectroscopy and gadolinium enhancement) will be obtained 
between L-75 and L-60 (a repeat between L-75 and launch in Russia will be required if a Russian landing 
is planned) and again at R+3 and between R+22 and R+30.  Graded tilt tests with ECG will be performed 
between L-75 and L-60 and again on R+0.  Exercise and medication logs will be obtained both before and 
after flight, preferably via data sharing. 
Category:  Human Research and Countermeasure Development for Exploration 
  
Subcategory: Cardiovascular & Respiratory Systems in Space 
 
Space Applications: Once the magnitude, time course, and inciting factors for cardiac atrophy have 
been determined, effective countermeasures currently being developed by the investigators in parallel 
ground-based experiments may be applied, focused on normalizing cardiac work and volume during long-
duration space flight.  Upon completion of these experiments, a number of important risks for long-
duration space flight, such as cardiac function and arrhythmia risk may either be deemed manageable by 
current preventive measures, or clearly defined for future countermeasure research.   
 
Earth Applications: The information obtained from these space flight experiments also may be relevant 
for patients after prolonged confinement to bedrest, or chronic reduction in physical activity, as well as for 
patients with disease processes that alter cardiac stiffness such as congestive heart failure, ischemic 
heart disease, and normal ageing.  
 
Manifest Status:  Planned 
 
Supporting Organization: Exploration Systems Mission Directorate (ESMD) 
 
Previous Missions: The investigators have extensive previous experience with cardiovascular 
investigations performed on Space Shuttle and Mir; however, this is a new experiment. 
 
Results: N/A 
 
Results Publications: N/A 
 
Related Publications 
Dorfman TA, Rosen BD, Perhonen MA, Tillery T, McColl R, Peshock RM, Levine BD. Diastolic Suction is 
Impaired by Bed Rest: MRI Tagging Studies of Diastolic Untwisting Journal of Applied Physiology. 2008; 
104(4):1037-1044. 
 
Lathers CM, Schraeder PL, Bungo MW. The Mystery of Sudden Death: Mechanisms for Risk.  Epilepsy 
and Behavior. 2008; 12: 3-24. 
 
Dorfman TA, Levine BD, Tillery T, Peshock RM, Hastings JL, Schneider SM, Macias BR, Biolo G, 
Hargens AR.  Cardiac atrophy in women following bed rest.  Journal of Applied Physiology. 2007 ;103-8-
16. 
 
Iwasaki K, Levine BD, Zhang R, Zuckerman JH, Pawelczyk JA, Diedrich A, Ertl AC, Cox JF, Giller CA, 
Ray CA, Lane LD, Buckey JC, Baisch F, Eckberg DL, Robertson D, Biaggioni I, Blomqvist G.  Human 
cerebral autoregulation before, during, and after spaceflight.  Journal of Physiology. 2007 ;579.3, 799-
810. 
 
Fu Q, Witkowski S, Okazaki K, Levine BD.  Effects of Gender and Hypovolemia on Sympathetic Neural 
Responses to Orthostatic Stress.  American Journal of Physiololgy. Regulatory, Integrative and 
Comparative Physiology. 2005 ;289, R109-R116. 
 
Bleeker MW, De Groot PCE, Pawelczyk JA, Hopman MTE, Levine BD.  Effects of 18 days of bed rest on 
leg and arm venous properties.  Journal of Applied Physiology. 200496: 840 – 847,. 
 
Arbab-Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thoma JD, Palmer DM, Levine BD.  Effect 
of Aging and Physical Activity on Left Ventricular Compliance. Circulation2004 ;110 (13):1799-1805. 
 
Martin DS, South DA, Wood ML, Bungo MW, Meck JV: Comparison of Echocardiographic Changes After 
Short- and Long-Duration Spaceflight.  Aviation  Space and Environmental Medicine. 2002 ;73(6):532-6. 
 
 Fu Q, Levine BD, Pawelczyk JA, Ertl AC, Diedrich A, Cox JF, Zuckerman JH, Ray CA, Smith ML, Iwase 
S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane L, Buckey J, Cooke W, Robertson R, Baisch 
F, Blomqvist G, Eckberg DL, Robertson D, Biaggioni I.  Cardiovascular and sympathetic neural responses 
to handgrip and cold pressor stimuli in humans before, during and after spaceflight.  The Journal of 
Physiolology. 2002 ;544.2:653-664. 
 
Levine BD, Pawelczyk JA, Ertl AC, Cox JF, Zuckerman JH, Diedrich A, Biaggioni I, Ray CA, Smith ML, 
Iwase S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane LD, Buckey Jr. JC, Cooke WH, Baisch 
FJ, Robertson D, Eckberg DL, Blomqvist CG.  Human muscle sympathetic neural and haemodynamic 
responses to tilt following spaceflight. Journal of Physiology. 2002 ;538:331-340.. 
 
Ertl AC, Diedrich A, Biaggioni I, Levine BD, Robertson RM, Cox JF, Zuckerman JH, Pawelczyk JA, Ray 
CA, Buckey JC, Lane LD, Shiavi R, Gaffney FA, Costa F, Holt C, Blomqvist CG, Eckberg D, Baisch FJ, 
Robertson D.  Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space.  
The Journal of Physiology. 2002 ;538:321-329. 
 
Cox JF, Tahvanainen K, Kuusela TA, Levine BD, Cooke WH, Mano T, Iwase S, Saito M, Sugiyama Y, 
Ertl AC, Biaggioni I, Diedrich A, Robertson RM, Zuckerman JH, Layne LD, Ray CA, White RJ, Pawelczyk 
JA, Buckey JC, Baisch FJ, Blomqvist CG, Robertson D, and Eckberg DL.  Influence of microgravity on 
astronaut's sympathetic and vagal responses to Valsalva's manoeuvre.  The Journal of Physiology. 2002 
;538:309-320. 
 
Pawelczyk JA, Zuckerman JH, Blomqvist CG, Levine BD.  Regulation of muscle sympathetic nerve 
activity after bed rest deconditioning.   The American Journal of Physiology, Heart and Circulatory 
Physiology. 2001 ;280(5):2230-2239. 
 
Perhonen M, Zuckerman JH, Levine BD.  Deterioration of left ventricular chamber performance after bed 
rest: "Cardiovascular deconditioning" or hypovolemia? Circulation. 2001; 103:1851-1857. 
 
Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist CG, Zerwekh JE, Peshock RM, Weatherall PT, 
Levine BD.  Cardiac atrophy after bed rest and spaceflight.  Journal of Applied Physiology. 2001 ;91:645-
653. 
 
Cooke WH, Ames JE, Crossman AA, Cox JF, Kuusel TA, Tahvanainen K, Levine BD, Moon B, Blomqvist 
CG,  Eckberg DL.  Nine months in space:  The effects on human autonomic cardiovascular regulation.  
Journal of Applied Physiology. 2000 ;89:1039-1045. 
 
Web Sites:  
ISS Medical Project 
https://hrf.jsc.nasa.gov/science/default.asp?e_id=101  
 
Institute for Exercise and Environmental Medicine 
www.ieemphd.org  
 
Related Payload(s): None 
 
 


Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

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