Effects of levosimendan on myocardial contractility and oxygen consumption

Koji Todaka, Jie Wang, Geng Hua Yi, Richard Stennett, Mathias Knecht, Milton Packer, Daniel Burkhoff

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47 Citations (Scopus)

Abstract

Levosimendan is hypothesized to be primarily a calcium sensitizer in vitro. Therefore, its inotropic action may be similar in both the normal and the congestive heart failure (CHF) state, and it may be associated with a decreased energetic cost of inotropism in vivo. To test these hypotheses, we gave levosimendan to cross-circulated isolated hearts from normal (n = 11) and CHF (n = 7, 4-week rapid pacing) dogs. Peak isovolumic left ventricular pressure at an end-diastolic pressure of 5 mm Hg (P(max,5)) measured by an intraventricular balloon was 120 ± 15 mm Hg in normal dogs, and it was increased by ~40% in response to ~0.63 μM levosimendan. In CHF dogs, base- line P(max,5)) was only 60 ± 12 mm Hg (P < .01 compared to normals), and ~8.4 μM levosimendan (P < .05) was required to increase P(max,5)) by ~40%. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and failing hearts. The blunted inotropic response in CHF and the energetic cost of inotropism were also comparable to those obtained with isoproterenol. In other studies, there was no significant inotropic action of levosimendan in Langendorff-perfused rat hearts (n = 5), and intracellular calcium concentration, estimated by macroinjected aequorin, in ferret hearts (n = 2) increased dose-dependently. These findings suggest that inotropic actions of levosimendan in vivo may be mediated in part by factors other than calcium sensitization.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume279
Issue number1
Publication statusPublished - Oct 1 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Todaka, K., Wang, J., Yi, G. H., Stennett, R., Knecht, M., Packer, M., & Burkhoff, D. (1996). Effects of levosimendan on myocardial contractility and oxygen consumption. Journal of Pharmacology and Experimental Therapeutics, 279(1), 120-127.