Effects of Levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure

Abstract Background Oxidative stress is associated with maladaptive cardiac remodeling and vascular dysfunction and may be an important contributor to chronic heart failure (CHF) deterioration. We sought to investigate if the calcium sensitizer levosimendan beneficially modulates circulating markers of oxidative and nitrosative stress thus lessening their deleterious effects in patients with advanced CHF. Methods Thirty-nine patients with advanced CHF (mean NYHA 3.5±0.4; ischemic/dilated: 23/16; mean left ventricular ejection fraction: 26±7%) who were hospitalized due to syndrome worsening, were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1μg/(kgmin) ( n =26) or placebo ( n =13). Plasma b-type natriuretic peptide (BNP), circulating markers of oxidative [protein carbonyls, malondialdehyde (MDA)] and nitrosative (nitrotyrosine) stress, and cyclic GMP (cGMP) were measured at baseline and 48h after each treatment. Results Baseline characteristics and medications were well balanced in the two treatment groups. A significant improvement in left ventricular ejection fraction ( P P P P Conclusion Levosimendan does not increase markers of oxidative and nitrosative stress in contrast to the placebo treatment, thus, exerting cardioprotective effects in advanced CHF patients. Moreover, levosimendan may exert its biologic action through non-cGMP-dependent biochemical pathways.