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Cited by 27Cardiac Ischemia and ReperfusionHeart Failure Treatment and ManagementCardiovascular Function and Risk Factors

Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium

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Hermann, H·2002·Cardiovascular Research
DOI 10.1016/s0008-6363(01)00437-0
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Abstract

BACKGROUND: Pyruvate has been shown to increase contractile function in isolated myocardium and to improve hemodynamics in patients with congestive heart failure. We tested the hypothesis that pyruvate potentiates the inotropic response to beta-adrenergic stimulation and to elevated extracellular calcium, since this may be of potential therapeutic value in the clinical setting of acute heart failure in order to circumvent deleterious effects on energy demand as can occur during catecholamine therapy. METHODS AND RESULTS: We investigated isometrically contracting isolated multicellular muscle preparations from terminal failing human hearts at 37 degrees C, pH 7.4, and a stimulation frequency of 1 Hz. At an extracellular calcium concentration of 1.25 mM, pyruvate (10 mM) alone increased developed force (F(dev)) from 9.0+/-2.3 to 21.1+/-4.3 mN/mm(2) (n=9, P<0.001) and isoproterenol (1 microM) alone increased F(dev) from 9.5+/-2.0 to 31.3+/-5.4 mN/mm(2) (P<0.001), whereas the combination of pyruvate and isoproterenol increased F(dev) over-proportionally from 9.0+/-2.3 to 47.4+/-6.4 mN/mm(2) (P<0.01). In a separate series we assessed the combination of pyruvate and calcium. Although F(dev) did not increase from 12 to 16 mM [Ca(2+)](o), 10 mM pyruvate further increased F(dev) from 25.8+/-5.0 to 30.6+/-4.7 mN/mm(2) (P<0.01). Rapid cooling contractures revealed that altered myofilament responsiveness and/or sarcoplasmic reticulum (SR) calcium load must underlie the positive inotropic effect of pyruvate. CONCLUSION: A combination of pyruvate and beta-adrenergic stimulation may be of therapeutic value in acute heart failure by reducing the concentrations of potential deleterious catecholamines that are currently necessary to maintain adequate tissue perfusion.

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  • In vitro contraction assessment in human cardiac tissue is a valuable tool for studying drugs or physiological processes.

    “Still, despite these difficulties, in vitro assessment of contraction in human cardiac tissue can be an important tool to study drugs or physiological processes (Hermann, et al., 2002; Janssen, et al., 1999; Janssen, et al., 2000; Pieske, et al., 1995; Rossman, et al., 2004).”

    From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Hermann, et al., 2002

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Research works printed but not linked: 6

  1. References tion. Basic Res Cardiol 1993;88:179-191.
  2. Hasenfuss G, Hermann P, Pieske B, Maier LS, Just H. Influence of cardiac muscle. Cardiovasc Res 1995;29:391-400. pyruvate on hemodynamics and calcium cycling in failing human
  3. Hermann HP, Pieske B, Schwarzmuller E, Keul J, Just H, Hasenfuss 1993;264(33):C761-C782.
  4. Hasenfuss G, Holubarsch Ch, Just H, Blanchard E, Mulieri LA, 1994;1224:22-32.
  5. on behalf of the ECLA Collaborative Group, Dıaz R, Paolasso EA, failing human hearts. New Engl J Med 1982;307:205-211.
  6. Pitschner HF, Droege A, Mitze M, Schlepper M, Brodde OE. tion. Circulation 1998;98:2227-2234.

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Authors
Hermann, H.
Affiliations
University of Göttingen (DE)
Corresponding author
Hermann, H
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2002-01
Volume
53
Issue
1
Pages
116-123
ISSN
0008-6363 (ISSN-L)
DOI
10.1016/s0008-6363(01)00437-0
OpenAlex
W2135409745
Cited by
27
References
37
Citations by year
2022: 1 · 2020: 1 · 2019: 1 · 2016: 1 · 2013: 3
FWCI
2.76
Type
journal article
Language
en
Open access
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
pyruvate, beta-adrenergic stimulation, inotropic effect, isoproterenol, extracellular calcium, acute heart failure, catecholamine therapy, sarcoplasmic reticulum calcium, cardiac contractility, energy metabolism
MeSH terms
Adrenergic beta-Agonists, Aged, Analysis of Variance, Calcium, Drug Synergism, Female, Heart Failure, Humans, Isoproterenol, Male, Middle Aged, Myocardial Contraction, Myocardium, Stimulation, Chemical, Statistics, Nonparametric, Pyruvic Acid, In Vitro Techniques

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