The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine

Eur J Heart Fail. 2005 Aug;7(5):882-7. doi: 10.1016/j.ejheart.2005.02.002.

Abstract

Aim: To investigate the effect of a new inotropic drug, levosimendan compared with dobutamine on levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and malondialdehyde (MDA) in patients with severe decompensated heart failure.

Methods and results: Twenty-nine consecutive patients (22 males and 7 females), mean age 70.5+/-9.9 years, with decompensated heart failure on standard medical therapy, were randomised to receive either a 24 h infusion of levosimendan (n=15) or dobutamine (n=14). Blood samples were drawn at baseline, 48 h and 5 days post infusion. Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01). MDA levels were significantly lower 5 days after levosimendan compared to baseline (2.3+/-0.2 vs 3+/-0.3 microM, p=0.01). TNF-alpha levels did not differ between the groups. The comparison of percentage alteration compared to baseline showed that BNP (-44.5+/-7.6% vs 4.8+/-18.7%, p=0.025), MDA (-21.8+/-5.1% vs 14.9+/-8.5%, p=0.001) and IL-6 (-38.8+/-12.5% vs 70.2+/-24%, p=0.001) levels were significantly lower in the levosimendan group 5 days after treatment compared to the dobutamine group.

Conclusions: Treatment with levosimendan in advanced decompensated heart failure exerts a beneficial hemodynamic, anti-inflammatory and antioxidant effect. These findings may give an insight into the favourable impact on mortality that levosimendan appears to have in published multicenter trials.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Aged
  • Aged, 80 and over
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology*
  • Dobutamine / pharmacology
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Humans
  • Hydrazones / administration & dosage
  • Hydrazones / pharmacology*
  • Infusions, Intravenous
  • Interleukin-6 / blood
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Oxidative Stress / physiology
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacology*
  • Simendan
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Adrenergic beta-Agonists
  • Cardiotonic Agents
  • Hydrazones
  • Interleukin-6
  • Pyridazines
  • Tumor Necrosis Factor-alpha
  • Natriuretic Peptide, Brain
  • Simendan
  • Dobutamine
  • Malondialdehyde