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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)
05.15.09

Overview | Description | Applications | Operations | Results | Publications | Images

Experiment/Payload Overview

Brief Summary

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 (decrease in the size of the heart muscle) associated with long-duration space flight. This experiment will also identify the mechanisms of this atrophy and the functional consequences for crewmembers who will spend extended periods of time in space.

Principal Investigator

  • 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)/Collaborator(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

    • Payload Developer

    Johnson Space Center, Human Research Program, Houston, TX

    Sponsoring Agency

    National Aeronautics and Space Administration (NASA)

    Expeditions Assigned

    |19|20|

    Previous ISS Missions

    This is a new investigation for the ISS, although the investigators have extensive experience with cardiovascular investigations performed on Space Shuttle and Mir.

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    Experiment/Payload Description

    Research Summary

    • Atrophy (a decrease) in the size of the heart muscle appears to develop during space flight and its ground-based analogues (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.


    • This experiment will determine how much cardiac atrophy occurs during space flight and how fast it develops, 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 reintroduction of 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 help to ensure crew health on future long-duration exploration missions and will assist in the development of any needed countermeasures to mitigate the effects of spaceflight on the cardiovascular system.

    Description

    Cardiac atrophy (a decrease in the size of the heart muscle) appears to develop during space flight or its ground-based analogues (bedrest), leading to diastolic dysfunction (abnormal left ventricular function in the heart) and orthostatic hypotension (drop in blood pressure upon standing). Such atrophy also may be a potential mechanism for the cardiac arrhythmias (irregular heart rhythms) identified in some crewmembers after long-duration exposure to microgravity aboard the Mir space station. Recent studies have 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. This experiment 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 under both normal (Earth) gravity and fractional gravity (Mars and 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 left and right ventricular atrophy associated with long-duration space flight (using magnetic resonance imaging or 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 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).

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    Applications

    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 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.

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    Operations

    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, and 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 echocardiograms using the HRF Ultrasound will be performed on FD14, FD30, FD135, and return minus 15-days (R-15) using real-time remote guidance. On FD75, an exercise echocardiogram 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, and 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 echocardiograms will be obtained between launch minus 21-days (L-21) and L-7 and again at return plus 7-days (R+7). An exercise echocardiogram will be performed between L-75 and L-60 and again at R+4 and R+14. Preflight, ambulatory blood pressure, holter, and 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, and 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 echocardiograms 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.

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    Results/More Information

    Information Pending

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    Related Web Sites
  • Institute for Exercise and Environmental Medicine

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    Publications

    Results Publications

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      Related Publications
      • 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. ;89:1039-1045. 2000
      • 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. ;91:645-653. 2001
      • Perhonen M, Zuckerman JH, Levine BD. Deterioration of left ventricular chamber performance after bed rest: "Cardiovascular deconditioning" or hypovolemia? Circulation. ;103:1851-1857. 2001
      • 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. ;280(5):2230-2239. 2001
      • 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. ;538:321-329. 2002
      • 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. ;538:331-340. 2002
      • 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. ;544.2:653-664. 2002
      • 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. ;73(6):532-6. 2002
      • 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. Circulation. ;110 (13):1799-1805. 2004
      • 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. ;96: 840 - 847. 2004
      • 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. ;289, R109-R116. 2005
      • 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. ;579.3, 799-810. 2007
      • 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. ;103-8-16. 2007
      • Lathers CM, Schraeder PL, Bungo MW. The Mystery of Sudden Death: Mechanisms for Risk. Epilepsy and Behavior. ;12: 3-24. 2008
      • 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. ;104(4):1037-1044. 2008

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      Images

      imageComputer generated diagram of the Integrated Cardiovascular investigation onboard the ISS. Image courtesy of the Johnson Space Center, Human Research Program.
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      imageCatherine (Cady) Coleman is performing a remotely guided echocardiogram on a test subject utilizing the Integrated Cardiovascular protocols, while Betty Chen, a training coordinator observes.
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      Information Provided and Updated by the ISS Program Scientist's Office
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