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.
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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
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Self-citation
Research works printed but not linked: 8
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Cited by
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From space to Earth: Advances in human physiology from 20 years of bed rest studies (1986–2006)
Pavy-Le Traon, A., Heer, M., Narici, M. V., Rittweger, J., & Vernikos, J. (2007) · European Journal of Applied Physiology · doi:10.1007/s00421-007-0474-z · Cited by 658
Effect of Aging and Physical Activity on Left Ventricular Compliance
Arbab-Zadeh, A., Dijk, E., Prasad, A., Fu, Q., Torres, P., Zhang, R., Thomas, J. D., Palmer, D., & Levine, B. D. (2004) · Circulation · doi:10.1161/01.cir.0000142863.71285.74 · Cited by 535
Self-citationCardiac atrophy after bed rest and spaceflight
Perhonen, M. A., Franco, F., Lane, L. D., Buckey, J. C., Blomqvist, C. G., Zerwekh, J. E., Peshock, R. M., Weatherall, P. T., & Levine, B. D. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.2.645 · Cited by 494
Self-citation: what do we know, and what do we still need to know?
Levine, B. D. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.147629 · Cited by 436
Self-citationGluckman, T. J., Bhave, N. M., Allen, L. A., Chung, E. H., Spatz, E. S., Ammirati, E., Baggish, A. L., Bozkurt, B., Cornwell, W. K., Harmon, K. G., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.02.003 · Cited by 431
Self-citation
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
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