Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart
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Objectives The objective of the present study was to determine whether improved contractility after left ventricular assist device (LVAD) support reflects altered myocyte calcium cycling and changes in calcium-handling proteins. Background Previous reports demonstrate that LVAD support induces sustained unloading of the heart with regression of pathologic hypertrophy and improvements in contractile performance. Methods In the human myocardium of subjects with heart failure (HF), with non-failing hearts (NF), and with LVAD-supported failing hearts (HF-LVAD), intracellular calcium ([Ca(2+)](i)) transients were measured in isolated myocytes at 0.5 Hz, and frequency-dependent force generation was measured in multicellular preparations (trabeculae). Abundance of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA), Na(+)/Ca(2+) exchanger (NCX), and phospholamban was assessed by Western analysis. Results Compared with NF myocytes, HF myocytes exhibited a slowed terminal decay of the Ca(2+) transient (DT(terminal), 376 +/- 18 ms vs. 270 +/- 21 ms, HF vs. NF, p Conclusions Improvement in rate-dependent contractility in LVAD-supported failing human hearts is associated with a faster decay of the myocyte calcium transient. These improvements reflect decreases in NCX abundance and transport capacity without significant changes in SERCA after LVAD support. Our results suggest that reverse remodeling may involve selective, rather than global, normalization of the pathologic patt…
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Increasing stimulation frequency in rabbit in vitro preparations from 1 to 4 Hz and human preparations from 0.5 to 2.5 Hz increases contractile force by about 120-200% and 81-168%, respectively.
“Increasing the stimulation frequency in rabbit (from 1 Hz to 4 Hz) and human in vitro muscle preparations (from 0.5 Hz to 2.5 Hz) results increase in contractile force of about 120–200% and 81–168%, respectively”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Chaudhary, et al., 2004
Both rabbit and human ventricles show robust positive force-frequency responses.
“Both rabbit and human ventricles exhibit robust positive force-frequency responses.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Chaudhary, et al., 2004
The force of isolated human cardiac trabeculae increases ~81-168% as stimulation frequency is increased from 0.5 Hz to 2.5 Hz.
“the force of isolated human cardiac trabeculae increases ~81–168% as the stimulation frequency is increased from 0.5 Hz to 2.5 Hz (Chaudhary, et al., 2004; Pieske, et al., 1996; Rossman, et al., 2004).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Chaudhary, et al., 2004
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References 39 · Cited by 95
- Authors
- Chaudhary, K. W., Rossman, E. I., Piacentino, V., Kenessey, A., Weber, C., Gaughan, J. P., Ojamaa, K., Klein, I., Bers, D. M., Houser, S. R., & Margulies, K. B.
- Affiliations
- Temple University (US)
- North Shore University Hospital (US)
- Loyola University Chicago (US)
- Corresponding author
- Margulies, Kenneth B.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 44
- Issue
- 4
- Pages
- 837-845
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2075947943
- Cited by
- 95
- References
- 39
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG017022, AG17022)
- National Heart, Lung, and Blood Institute (R01HL061495, HL-33921, HL 61495, HL-03560)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- left ventricular assist device, heart failure, calcium transients, Na+/Ca2+ exchanger, SERCA, phospholamban, reverse remodeling, cardiac contractility, force-frequency relationship, sarcoplasmic reticulum, myocardial unloading
- MeSH terms
- Phospholamban, Calcium-Transporting ATPases, Calcium, Calcium-Binding Proteins, Female, Heart Failure, Heart-Assist Devices, Humans, Male, Middle Aged, Myocardial Contraction, Blotting, Western, Case-Control Studies, Sodium-Calcium Exchanger, Myocytes, Cardiac, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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