title: The inhibitory in-vitro effect of high-dose levosimendan on platelet function may be mediated through its action as a phosphodiesterase inhibitor.
abstract: OBJECTIVE
  Levosimendan enhances cardiac contractility by increasing myocyte sensitivity to calcium and causing vasodilatation. Although studies have evaluated the efficacy of levosimendan in heart failure, whether levosimendan produces an effect on platelets is a subject of controversy. In the present study, the in-vitro effect of levosimendan on platelet aggregation was investigated. The effect of levosimendan on the cyclic AMP concentration was determined according to its second mode of action as a selective phosphodiesterase III inhibitor.
  
  
  METHODS
  Platelet aggregation setting was performed using venous blood from three healthy volunteers. Different concentrations of levosimendan solution were prepared that would result in 0.04-125 µg/ml levosimendan concentrations in whole blood and in platelet-enriched plasma. After incubation for 3 min at 37°C, aggregation responses were evaluated with ADP (10 µmol/l), collagen (5 µg/ml), or NaCl. The cyclic AMP concentration was determined using the enzyme-linked immunosorbent assay technique.
  
  
  RESULTS
  The in-vitro results clearly showed that there was only a relationship between a high levosimendan concentration (12-125 µg/ml) and inhibition of platelet aggregation that was negatively dependent on the cAMP concentration.
  
  
  CONCLUSIONS
  Levosimendan has no significant effect as a phosphodiesterase III inhibitor on in-vitro platelet aggregation in clinically relevant doses.
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany. konstanze.plaschke@med.uni-heidelberg.de
authors.forename: Konstanze
authors.initials: K
authors.lastname: Plaschke
authors.forename: Franziska
authors.initials: F
authors.lastname: Bent
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenhagen
authors.forename: Sören
authors.initials: S
authors.lastname: Wagner
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kopitz
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D000077464:Simendan
chemical_list: D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan; D000242:Cyclic AMP