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Cited by 371Spaceflight effects on biologyCardiovascular Syncope and Autonomic DisordersCardiovascular and exercise physiology

Cardiac Atrophy After Bed-Rest Deconditioning: A Nonneural Mechanism for Orthostatic Intolerance

Levine, Benjamin D., Zuckerman, Julie H., Pawelczyk, James A.·1997·Circulation
DOI 10.1161/01.cir.96.2.517
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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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  • The same mechanisms described in space flight have also been seen following prolonged bedrest deconditioning.

    “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]

  • 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.

    “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]

  • The decrease in stroke volume was out of proportion to the degree of plasma volume reduction, as predicted by the Starling curve.

    “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 POTS, the physiological reactions to orthostatic stress are similar to those seen in deconditioning from prolonged bed rest or space flight, including tachycardia, exercise intolerance, and lower left ventricular mass, stroke volume, and blood volume.

    “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

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Authors
Levine, B. D., Zuckerman, J. H., & Pawelczyk, J. A.
Affiliations
  • Texas Health Dallas (US)
  • Pennsylvania State University (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1997-07-15
Volume
96
Issue
2
Pages
517-525
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.96.2.517
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 › Spaceflight effects on biology
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Complementary and alternative medicine › 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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