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Cited by 84Cardiac electrophysiology and arrhythmiasCardiovascular Function and Risk FactorsCardiac Ischemia and Reperfusion

Abnormal frequency-dependent responses represent the pathophysiologic signature of contractile failure in human myocardium

Rossman, E·2004·Journal of Molecular and Cellular Cardiology
DOI 10.1016/j.yjmcc.2003.09.001
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Abstract

Background - The normal increase in isometric developed force (DF) with faster pacing rates, known as the positive force-frequency response/relationship (FFR), is altered in failing myocardium, as shown by its negative response to increased pacing. The objective of this study was to determine if increasing Ca2+ influx with L-type Ca2+ channel (L-CaCh) agonists: BayK 8644 (BayK) and FPL 64176 (FPL) or increased extracellular Ca2+ could increase contractility and normalize the FFR in failing myocardium.Methods - Isometric DF was measured in right ventricular trabeculae from failing (n = 28) and non-failing (n = 12) human hearts at various stimulation frequencies (0.5-2.5 Hz) before and after bath application of BayK (250 nM), FPL (100 nM), or high Ca2+ (7.0 mM). Post-rest (PR) experiments were also conducted on several trabeculae.Results - In trabeculae from failing hearts, the DF decreased with an increase in pacing. Addition of L-CaCh agonists increased DF to similar levels in trabeculae from both failing and non-failing hearts at slow pacing rates, but did not alter the negative FFR in the failing group. During increased rest intervals, the amount of PR potentiation was diminished in trabeculae from failing hearts as compared to the non-failing preparations.Conclusion - This study demonstrates that the abnormal FFR observed in trabeculae from failing hearts is a reliable physiologic signature of the cardiomyopathic state even when DF, at slow stimulation frequencies, is relatively high. These studies further demonstrate that the impaired FFR is not due to an inability to further increase contractility. Rather, our findings suggest that the abnormal FFR and blunted PR potentiation alike are a reflection of an altered functional balance between Ca2+ re-uptake and Ca2+ extrusion.

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  • 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 Rossman, et al., 2004

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Authors
Rossman, E.
Affiliations
Temple University (US)
Corresponding author
Rossman, E
ORCID
Rossman, E
Venue
Journal of Molecular and Cellular Cardiology
Publisher
Elsevier BV
Published
2004-01
Volume
36
Issue
1
Pages
33-42
ISSN
0022-2828 (ISSN-L)
DOI
10.1016/j.yjmcc.2003.09.001
OpenAlex
W2054120564
Cited by
84
References
37
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 5 · 2012: 6
FWCI
3.09
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Molecular and Cellular Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Temple University
  • National Institutes of Health
  • National Institute on Aging (R01AG017022, AG17022)
  • National Heart, Lung, and Blood Institute (R01HL061495, HL-33921, HL 61495, HL-03560)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
force-frequency relationship, contractile failure, L-type calcium channel agonist, Bay K 8644, extracellular calcium, post-rest potentiation, right ventricular trabeculae, cardiomyopathy
MeSH terms
Calcium, Calcium Channel Agonists, Heart, Heart Defects, Congenital, Heart Failure, Humans, Isometric Contraction, Myocardial Contraction, Myocardium, Calcium Channels, L-Type

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