© 2005 European Society of Cardiology
The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine
a State Cardiology Department Hippokration Hospital, 114 Vassilissis Sophias, Athens, Greece
b Laboratory of Biopharmaceutics and Pharmacokinetics School of Pharmacy, University of Athens, Panepistimiopolis 15771, Athens, Greece
* Corresponding author. Tel.: +30 210 7274827; fax: +30 210 7274747.
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Abstract |
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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-
), 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 µM, p=0.01). TNF- 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.
Key Words: Levosimendan • Heart failure • Dobutamine • Oxidative damage • BNP • Pro-inflammatory cytokines
Received July 6, 2004; Revised December 22, 2004; Accepted February 8, 2005
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