The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Cardiac Atrophy After Bed-Rest Deconditioning: A Nonneural Mechanism for Orthostatic Intolerance
Abstract
Background The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. Methods and Results We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with −6° head-down tilt (n=12 subjects aged 24±5 years). Pressure (P)-volume (V) curves were modeled exponentially by P= ae k V + b and logarithmically by P=− S ln[(V m −V)/(V m −V 0 ], where V 0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V 0 (33%), and orthostatic tolerance (24%) (all P <.05). The slope of the SV/PCWP curve increased from 4.6±0.4 to 8.8±0.9 mL/mm Hg ( P <.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% ( P <.10). Conclusions Two weeks of head-down–tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“These same mechanisms described in space flight have also been seen following prolonged bedrest deconditioning (23,(25)(26)(27).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [23]
In the citing paper
“Under normal gravitational conditions, two weeks of strict bedrest resulted in a 17% reduction in plasma volume and a near 10% reduction in stroke volume (41).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [41]
In the citing paper
“The decrease in stroke volume, as predicted by the Starling curve, was out of proportion to the degree of plasma volume reduction (41).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [41]
In the citing paper
“The physiological responses to orthostatic stress in POTS often resemble the clinical phenotype of patients with deconditioning from prolonged bed rest or space flight (e.g.tachycardia, exercise intolerance, and reductions in left ventricular mass, stroke volume, blood volume) (Fu et al., 2010a;Levine et al., 1997;Tank et al., 2011).”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Levine et al., 1997
Citations
Cites
Recommendations for Quantitation of the Left Ventricle by Two-Dimensional Echocardiography
Schiller, N. B., Shah, P. M., Crawford, M., DeMaria, A. N., Devereux, R. B., Feigenbaum, H., Gutgesell, H. P., Reichek, N., Sahn, D. J., Schnittger, I., et al. (1989) · Journal of the American Society of Echocardiography · doi:10.1016/s0894-7317(89)80014-8 · Cited by 8,110
Heart Disease: A Textbook of Cardiovascular Medicine.
(1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-3-415_3 · Cited by 4,119
Body composition from fluid spaces and density: analysis of methods. 1961.
Siri, W. E. (1994) · PubMed · Cited by 2,556
Handbook of Physiology—The Cardiovascular System
Guyton, A. C. (1985) · Critical Care Medicine · doi:10.1097/00003246-198505000-00025 · Cited by 1,153
Cardiac Contraction and the Pressure-Volume Relationship
SAGAWA, K. (1988) · Cited by 648
Cardiac Contraction and the Pressure-Volume Relationship
佐川, 喜. (1988) · Cited by 642
Orthostatic intolerance after spaceflight
Buckey, J. C., Lane, L. D., Levine, B. D., Watenpaugh, D. E., Wright, S. J., Moore, W. E., Gaffney, F. A., & Blomqvist, C. G. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.1.7 · Cited by 596
Self-citationPrinciples and Practice of Echocardiography
Weyman, A. E. (1994) · Medical Entomology and Zoology · Cited by 556
Assessment of diastolic function: suggested methods and future considerations.
MIRSKY, I. (1984) · Circulation · doi:10.1161/01.cir.69.4.836 · Cited by 405
Levine, B. D., Lane, L. D., Buckey, J. C., Friedman, D. B., & Blomqvist, C. G. (1991) · Circulation · doi:10.1161/01.cir.84.3.1016 · Cited by 320
Self-citation
Flagged first, then by citations
Research works printed but not linked: 8
- Blomqvist CG Levine BD Lane LD Buckey JC. Space medicine and physiology. In: Braunwald E ed. Current Medicine: Atlas of Heart Diseases. Philadelphia Pa: Mosby Inc; 1996;6:10.1-10.29.
- 10.1161/circ.69.4.6697466 · DOI
- Pawelczyk JA Levine BD Prisk GK Shykoff BE Elliot AR Rosow E. Accuracy and precision of flight systems for determination of cardiac output by soluble gas rebreathing. In: Proceedings of the 1995 NASA/AIAA Life Sciences and Space Medicine Conference; October 1995; Houston Tex: LS95-LS130:XII.
- 10.1161/circ.84.3.1884438 · DOI
- 10.1161/res.62.6.3383365 · DOI
- 10.1161/res.75.3.8062416 · DOI
- 10.1161/circ.87.4.8462159 · DOI
- 10.1161/res.70.1.1727683 · DOI
Cited by
Sorted by citations
Items 301–370 of 370
Wotring, V. E. (2012) · SpringerBriefs in space development · doi:10.1007/978-1-4614-3396-5_6 · Cited by 2
Beyond postural tachycardia syndrome
Mustafa, H. I., & Robertson, D. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.180620 · Cited by 2
Ade, C. J., & Wong, B. J. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90325.2008 · Cited by 2
Renal, Endocrine, and Cardiovascular Responses to Bed Rest in Male Subjects on a Constant Diet
Grenon, S. M., Sheynberg, N., Hurwitz, S., Xiao, G., Ramsdell, C. D., Ehrman, M. D., Mai, C. L., Rostoft, S., Sundby, G. H., Cohen, R. J., et al. (2004) · Journal of Investigative Medicine · doi:10.1177/108155890405200221 · Cited by 2
Zhang, X., Zhou, X., Tu, Z., Qiang, L., Lü, Z., Xie, Y., Liu, C. H., Zhang, L., & Fu, Y. (2024) · PLoS ONE · doi:10.1371/journal.pone.0313519 · Cited by 1
McKenna, Z. J., Sarma, S., Atkins, W. C., Gideon, E. A., McNary, J. L., & Crandall, C. G. (2025) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00276.2025 · Cited by 1
Priyanshu, P., Karim, A., Viswanath, V., Ramani, D. P., Fernandes, D., Miriyala, R., & Alapati, N. (2026) · Indian Journal of Palliative Care · doi:10.25259/ijpc_440_2025 · Cited by 1
Wu, B., Liu, Y., Sun, H., Zhao, D., Wang, Y., Wu, P., & Ni, C. (2010) · Acta Astronautica · doi:10.1016/j.actaastro.2010.05.005 · Cited by 1
Integrative Approach of Venous Return And Cardiac Output in the Context of Skeletal Muscle Atrophy
Restini, C. B. A. (2014) · Journal of Clinical & Experimental Cardiology · doi:10.4172/2155-9880.1000355 · Cited by 1
Vegetative and autonomic dysfunctions
Selzer, M. E., Clarke, S., Cohen, L. G., Kwakkel, G., & Miller, R. H. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9780511995590.035 · Cited by 1
Physiologic and Molecular Responses of the Heart to Chronic Exercise
Levine, B. D., & Buttrick, P. M. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381510-1.00024-7 · Cited by 1
Self-citationCardiovascular Deconditioning and Exercise
Stenger, M. B., Laurie, S. S., Lee, S. M. C., & Platts, S. H. (2021) · Springer eBooks · doi:10.1007/978-3-319-12191-8_20 · Cited by 1
Aerospace biomedical testing and future development
Yang, C., AnYi, L. I., Lv, X., Zhao, L., Zou, Y., Zhe, L. I., Li, X., Zhang, Y., Li, N., Chen, Z., et al. (2023) · Scientia Sinica Technologica · doi:10.1360/sst-2022-0416 · Cited by 1
Hbaieb, M. A., Charfeddine, S., Driss, T., Bosquet, L., Dugué, B., Abid, L., & Hammouda, O. (2025) · Archives of Rehabilitation Research and Clinical Translation · doi:10.1016/j.arrct.2025.100454 · Cited by 1
Cardiac Plasticity in Health and Disease
Gondalia, R., Rothermel, B. A., Lavandero, S., Gillette, T. G., & Hill, J. A. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-891-7_7 · Cited by 1
The declined phosphorylation of Heat shock protein 27 in rat cardiac muscle after hindlimb unloading
Yuan, M., Jiang, S., Li, Z., Yuan, M., Ting, L., Zhang, Y., & Wang, D. (2009) · Advances in Space Research · doi:10.1016/j.asr.2009.03.004 · Cited by 1
Surve, D., & Patil, P. (2019) · Biomedical & Pharmacology Journal · doi:10.13005/bpj/1644 · Cited by 1
Cardiovascular Deconditioning and Exercise
Stenger, M. B., Laurie, S. S., Lee, S. M. C., & Platts, S. H. (2020) · Springer eBooks · doi:10.1007/978-3-319-10152-1_20-2 · Cited by 1
Effects of gravity and posture on the human cardiovascular system
Bhaskaran, S., Mondal, S., Jagtap, S. S., & Vidyasagar, P. B. (2009) · Cited by 1
Steigele, W. (2020) · Springer eBooks · doi:10.1007/978-3-662-60538-7_12 · Cited by 1
Mathias, C. J., & Low, D. A. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9780511995590.037 · Cited by 1
Effects of supine and -6° head-down tilt posture on cardiovascular and exercise performance
Ade, C. J. (2008) · K-State Research Exchange (Kansas State University) · Cited by 1
Kinematic Characterization of Left Ventricular Chamber Stiffness and Relaxation
Mossahebi, S. (2014) · PubMed · doi:10.7936/k7hm56k3
Hutchings, S., Kim, J. M., Song, D., & Pang, C. C. Y. (2010) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y10-083
Meck, J. V., Stenger, M. B., Platts, S. H., & Ziegler, M. G. (2007) · NASA STI Repository (National Aeronautics and Space Administration)
Physical fitness and training in chronic childhood conditions
van Brussel, M. (2009) · Tijdschrift voor kindergeneeskunde · doi:10.1007/bf03086355
The effects of 60 days of head down bed rest on vascular health
Mattar, L. (2006) · UWSpace (University of Waterloo)
Cardiovascular Effects of Hind-limb Unweighing in Mice
Lee, Y. B., Park, J. T., Lim, H. K., Choi, J. C., Kim, S. Y., Cho, J. H., & Lee, K. H. (2007) · Korean Journal of Anesthesiology · doi:10.4097/kjae.2007.53.2.222
Heat Production During Countermeasure Exercises Planned for the International Space Station
Rapley, M. G., & Guilliams, M. E. (2004) · NASA Technical Reports Server (NASA)
Lung function in micro- and in hypergravity
Montmerle, S. (2005) · Figshare
Hao, W. Y., Bai, J.-Y., Zhang, W. Y., Wu, X., & Zhang, L. F. (2002) · Computers in cardiology · doi:10.1109/cic.2001.977664
TO LOWER BODY NEGATIVE PRESSURE (LBNP)
Mikulski, T., Cybulski, G., Ziemba, A. W., & Niewiadomski, W. (2006)
Rebuttal from Yellin and Nikolic
Yellin, E. L., & Nikolic, S. D. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01399.2009c
Beavers, K. R. (2009) · UWSpace (University of Waterloo)
Cardiorespiratory and vascular function during stress
Ade, C. J. (2013) · K-State Research Exchange (Kansas State University)
Grinberg, A. (2010) · UWSpace (University of Waterloo)
Joint Hypermobility Syndrome and Dysautonomia
Jacob, G., & Grubb, B. P. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-386525-0.00111-6
McCarthy, C. (2016) · Scholarship@Western (Western University)
nasa (2018)
Hoffen will Glück: Epikurs neuer Garten
Hüllemann, K.-D. (2020) · Springer eBooks · doi:10.1007/978-3-662-61407-5_9
Effect of In-Flight Exercise and Extravehicular Activity on Postflight Stand Tests
Lee, S. M. C., Moore, A., Fritsch-Yelle, J. M., Greenisen, M. C., Schneider, S. M., & Foster, P. P. (2000) · NASA Technical Reports Server (NASA)
Tay, M. R. J., Thio, J. M. L., Low, Y. H., Lau, S. W. T., & Chan, W. L. W. (2021) · International Journal of Therapy and Rehabilitation · doi:10.12968/ijtr.2020.0166
Beckers, F., Verheyden, B., & AUBERT, A. E. (2006) · Wiley Encyclopedia of Biomedical Engineering · doi:10.1002/9780471740360.ebs1107
Steigele, W. (2015) · Springer eBooks · doi:10.1007/978-3-662-47271-2_11
Prisk, G. K., Paiva, M., & West, J. B. (2001) · Lung biology in health and disease · doi:10.1201/b15295-13
Pizzolitto, K. S., Lalande, S., & Hughson, R. L. (2004) · International Astronautical Congress (IAC) · doi:10.2514/6.iac-04-g.p.07
Critical power (CP) testing: An accurate rapid method of fitness assessment during space missions
Jordan, S. L., Kern, J., Chilek, D. R., & Moore, A. (2022) · Acta Astronautica · doi:10.1016/j.actaastro.2022.05.049
The autonomic nervous system in space exploration
Appenzeller, O., Lamotte, G. J., & Coon, E. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-96011-3.00005-x
Dynamics of ST2 biomarker level under the influence of spaceflight and landing factorsPreprint
Pastushkova, L. K., Goncharov, I., Goncharova, A., Kashirina, D. N., Popova, O. V., & Larina, I. (2023) · Research Square · doi:10.21203/rs.3.rs-3009181/v1
Space Countermeasures and Medicine - Implementation into Earth medicine and Rehabilitation
(2023) · Frontiers research topics · doi:10.3389/978-2-8325-2592-0
Toro, M. R., Carvajalino‐Galeano, A. B., Pinto‐Brito, C., Múñoz, Ó., & García-Peña, Á. A. (2024) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.13116
Nobahar, M., Ahmadi, F., & Harijani, S. M. (2024) · Journal of Shahrekord University of Medical Sciences · doi:10.34172/jsums.894
Zhou, M., Zha, F., Zhao, L., Li, D., Luo, J., Wang, Y., Liu, F., Zhou, J., Zhang, Z., Zou, Y., et al. (2024) · International Journal of Clinical Practice · doi:10.1155/2024/2047103
Ghosh, G., Pipraiya, R., & Sinha, B. (2025) · Indian Journal of Aerospace Medicine · doi:10.25259/ijasm_8_2023
Chaudhury, D., Atia, N., Obiechina, N., Gill, A., Michael, A., & Sampathy, K. (2025) · Cureus · doi:10.7759/cureus.97581
MicroRNAs in space: biomarkers for health risk assessment and targets for countermeasures
Geng, D., Pal, B., Pradeep, N., Hajj, J. P., Amorim, T., Zaksas, V., Sharma, P., Sathipati, S. Y., Sahu, A., Singh, K., et al. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-32904-3.00002-9
Hirasawa, A., Washio, T., Suda, T., Hirabuki, K., Fukuie, M., Saito, S., Hata, N., Matsuda, T., Sugawara, J., Ogoh, S., et al. (2026) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00181.2025
Dumais, R., Suckow, E., Ainab, I., Zirille, F. M., Forbes, L. M., Lawley, J. S., & Cornwell, W. K. (2026) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph23050594
Robin, A., Reinarz, C., Pentinat-Llurba, H., Zaman, S. Y., Rasmussen, C. J., McKnight, J. R., Haddad, L., Zawieja, D. C., & Diaz‐Artiles, A. (2026) · Experimental Physiology · doi:10.1113/ep093840
Tripoli, F., Ridolfi, L., Romanelli, M., Rabbito, R., Roatta, S., & Scarsoglio, S. (2026) · European Journal of Applied Physiology · doi:10.1007/s00421-026-06313-7
Rabineau, J., Darwish, F. M. A., Mulder, E. R., Coolen, B. F., Hoffmann, F., Hautemann, D. J., Tank, J., Migeotte, P., Strijkers, G. J., & Wüst, R. C. I. (2026) · Experimental Physiology · doi:10.1113/ep093671
Wu, Z., Hou, H., Huang, Y. Q., Guo, F., Huang, S., Liu, Y., Wang, R. Y., Biekan, J., Zhao, P., Ren, P., et al. (2026) · Fluids and Barriers of the CNS · doi:10.1186/s12987-026-00845-y
Kwok, C. S., Hinton, J., Lip, G. Y. H., Qureshi, A. I., & Borovac, J. A. (2026) · Coronary Artery Disease · doi:10.1097/mca.0000000000001667
Postural Orthostatic Tachycardia Syndrome (POTS)
Chung, T., & Raj, S. R. (2026) · JAMA · doi:10.1001/jama.2026.14809
Yamazaki, T., MANCINI, D. M., Blate, M., Quan, P., Norweg, A. M., Cook, D. B., & Natelson, B. H. (2026) · Physiological Reports · doi:10.14814/phy2.71087
Appadurai, V., Negishi, K., Borowski, A. G., Popović, Z., Greenberg, N. L., Martin, D. S., Bungo, M. W., Levine, B. D., & Thomas, J. D. (2026) · Circulation · doi:10.1161/circulationaha.125.078665
Self-citationFedchuk, M. V., Popova, O. V., & Русанов, В. Б. (2026) · Extreme Medicine · doi:10.47183/mes.2026-542
The Necessity of Acute Phase Rehabilitation Treatment
Sato, C., & Yamauchi, K. (2026) · リハビリテーション医学 : 日本リハビリテーション医学会誌 · doi:10.2490/jjrmc.63.734
Metadata
- Authors
- Levine, B. D., Zuckerman, J. H., & Pawelczyk, J. A.
- Affiliations
- Texas Health Dallas (US)
- Pennsylvania State University (US)
- Venue
- Circulation
- Published
- 1997-07-15
- Volume
- 96
- Issue
- 2
- Pages
- 517-525
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2062414497
- Cited by
- 371
- References
- 48
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 11 · 2023: 17 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 13 · 2017: 15 · 2016: 8 · 2015: 14 · 2014: 16 · 2013: 13 · 2012: 20
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01RR000633, MO-1 RR-00633)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Spaceflight effects on biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- cardiac deconditioning, bed rest, orthostatic intolerance, stroke volume, left ventricular compliance, pressure-volume relationship, Starling curve, left ventricular mass, plasma volume, head-down tilt, lower body negative pressure, pulmonary capillary wedge pressure, left ventricular end-diastolic volume
- MeSH terms
- Adaptation, Physiological, Adolescent, Adult, Bed Rest, Blood Pressure, Cardiac Output, Cardiac Volume, Female, Humans, Male, Ventricular Function, Left, Cardiovascular Deconditioning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
