PT  - JOURNAL ARTICLE
AU  - Peter Bokník
AU  - Joachim Neumann
AU  - Grit Kaspareit
AU  - Wilhelm Schmitz
AU  - Hasso Scholz
AU  - Ute Vahlensieck
AU  - Norbert Zimmermann
TI  - Mechanisms of the Contractile Effects of Levosimendan in the Mammalian Heart
DP  - 1997 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 277--283
VI  - 280
IP  - 1
4099  - http://jpet.aspetjournals.org/content/280/1/277.short
4100  - http://jpet.aspetjournals.org/content/280/1/277.full
SO  - J Pharmacol Exp Ther1997 Jan 01; 280
AB  - In spontaneously beating guinea pig right atria, levosimendan (LS, or R-[[-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-phenyl]-hydrazono]propanedinitrile) exerted a positive chronotropic effect starting at 0.1 μM. In electrically driven guinea pig left atria, LS (0.1–10 μM) increased force of contraction without changing time parameters of contraction. In electrically driven right papillary muscles, LS (0.1–10 μM) enhanced force of contraction without affecting time parameters of contraction. The maximal effect on force of contraction at 10 μM amounted to 130 ± 8.6% of predrug value. The positive inotropic effect of LS in papillary muscles was greatly diminished by additionally applied carbachol. In [32P]-labeled guinea pig ventricular cardiomyocytes, LS increased the phosphorylation state of phospholamban, the inhibitory subunit of troponin and C-protein. The maximal effect at 1 μM amounted to 134 ± 8.6%, 124 ± 4.2% and 121 ± 8% of control for phospholamban, the inhibitory subunit of troponin and C-protein, respectively. LS (1 μM) increased cAMP content from 6.3 ± 0.3 to 8.1 ± 0.3 pmol/mg protein in guinea pig ventricular cardiomyocytes. Furthermore, whole-cell patch-clamp studies were performed in guinea pig ventricular cardiomyocytes. In this setup, 10 μM LS increased the amplitude of L-type Ca++ current to 402 ± 86% of predrug value. The American Society for Pharmacology and Experimental Therapeutics