The cardiotonic effects of levosimendan in guinea pig hearts are modulated by β-adrenergic stimulation

A. Bódi, S. Szilágyi, I. Édes, Z. Papp

Research output: Contribution to journalArticle

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Abstract

The effects of the Ca2+ -sensitiser levosimendan alone or in combination with β-adrenergic stimulation on the contractile function were studied in various guinea pig cardiac preparations. Echocardiography in narcotised animals indicated that a maximal dose of levosimendan (50 μg·kg-1) increased the left ventricular posterior wall movement velocity during systoles and diastoles by 25 ± 3% (mean ± S.E.M.) and 17 ± 2%, respectively. In Langendorff hearts, a saturating concentration of levosimendan (0.3 μmol·l-1 for 5 min) increased +dP/dtmax and -dP/dtmax by 28 ± 3% and 14 ± 2%, respectively. Further, the Ca2+ -sensitising potential of levosimendan in Triton-skinned cardiomyocytes (EC50: 5 ± 3 nmol·l-1) was illustrated by a maximal increase in the isometric force production by 51 ± 5% (at pCa 6.2). However, following stimulation by isoproterenol, when the level of troponin I phosphorylation was elevated, no significant additional increase in the contractile parameters could be demonstrated upon levosimendan administration. Moreover, the levosimendan-induced increase in force production in isolated skinned myocytes could be prevented by incubation with the catalytic subunit of protein kinase A (100 U·ml-1 for 40 min). These data indicate that thin filament-targeted Ca2+- sensitisation by levosimendan is modulated by phosphorylation of the contractile filaments, an effect that should be considered during combination therapy with levosimendan.

Original languageEnglish
Pages (from-to)313-327
Number of pages15
JournalGeneral Physiology and Biophysics
Volume22
Issue number3
Publication statusPublished - Sep 2003

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Cardiotonic Agents
Adrenergic Agents
Guinea Pigs
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Phosphorylation
Troponin I
simendan
Isoproterenol
Cardiac Myocytes
Muscle Cells
Echocardiography

Keywords

  • Ca-sensitisers
  • Cardiomyocytes
  • Contractility
  • Heart
  • Levosimendan

ASJC Scopus subject areas

  • Physiology
  • Biophysics

Cite this

The cardiotonic effects of levosimendan in guinea pig hearts are modulated by β-adrenergic stimulation. / Bódi, A.; Szilágyi, S.; Édes, I.; Papp, Z.

In: General Physiology and Biophysics, Vol. 22, No. 3, 09.2003, p. 313-327.

Research output: Contribution to journalArticle

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