Effects of Levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure.
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 0.1 microg/(kg min) (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 48 h 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<0.01), NYHA class (P<0.01), and plasma BNP (P<0.01) was observed post-treatment only in the levosimendan group. Markers such as MDA, protein carbonyls and nitrotyrosine remained stable in the levosimendan-treated group, but significantly increased (P<0.05) in the placebo-treated patients. Neither therapeutic intervention changed the levels of circulating cGMP.


CONCLUSIONS
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.
Parissis
John T
JT
Heart Failure Unit, Attikon University Hospital, Athens, Greece.
Andreadou
Ioanna
I
Markantonis
Sophia L
SL
Bistola
Vasiliki
V
Louka
Asimina
A
Pyriochou
Anastasia
A
Paraskevaidis
Ioannis
I
Filippatos
Gerasimos
G
Iliodromitis
Efstathios K
EK
Kremastinos
Dimitrios Th
DT
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013318:Stroke Volume / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D006835:Hydrazones; D011724:Pyridazines; D009569:Nitric Oxide; D000077464:Simendan; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde