Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure

Eur J Heart Fail. 2006 Dec;8(8):804-9. doi: 10.1016/j.ejheart.2006.03.003. Epub 2006 May 19.

Abstract

Background: The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown.

Aim: To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure.

Methods: Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double-blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion.

Results: Seven patients (1 levosimendan, 6 placebo), were excluded during follow-up. In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion. Serum sTNF-R2 was decreased at 24 h (p<0.05 vs baseline) and remained lower than baseline for at least 7 d (p<0.05).

Conclusions: These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-alpha receptors and sFAS, immediately after infusion, an effect which persists for 7-30 d.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Humans
  • Hydrazones / administration & dosage
  • Hydrazones / pharmacology*
  • Hydrazones / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Infusions, Parenteral
  • Interleukin-6 / blood
  • Male
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacology*
  • Pyridazines / therapeutic use*
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Simendan
  • Solubility
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • fas Receptor / metabolism*

Substances

  • Hydrazones
  • Interleukin-6
  • Pyridazines
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Simendan