Effects of levosimendan on flow-mediated vasodilation and soluble adhesion molecules in patients with advanced chronic heart failure.
OBJECTIVE
Endothelial activation and dysfunction may be an important contributor to chronic heart failure (CHF) progression. We sought to investigate whether the calcium sensitizer levosimendan affects beneficially endothelial function and attenuates the deleterious effects of soluble adhesion molecules in patients with advanced CHF.


METHODS
Twenty-six advanced CHF patients (mean New York Heart Association class, 2.6+/-0.3; ischemic/dilated, 18/8; mean left ventricular ejection fraction <35%) hospitalized due to syndrome worsening, were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1 microg/kg/min (n=17) or placebo (n=9). Endothelial function estimated by endothelial-dependent flow-mediated dilatation of the brachial artery (FMD), as well as plasma soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), were assessed before and 48 h after therapy.


RESULTS
Baseline characteristics and medications were well balanced in the two treatment groups. A significant improvement of FMD (6.4+/-4.4% from 4.8+/-3.0%; p<0.05) with concomitant reduction of plasma concentrations of sICAM-1 (231+/-75 pg/ml from 339+/-157 pg/ml; p<0.05) and sVCAM-1 (1134+/-508 pg/ml from 1386+/-602 pg/ml; p<0.05) were observed only in levosimendan treated patients.


CONCLUSIONS
Levosimendan could be an effective treatment in improving the endothelial function and reducing the detrimental adhesion molecule activation in advanced CHF patients.
Parissis
John T
JT
Second Department of Cardiology, Attikon University Hospital, Rimini 1, 12461 Chaidari, Athens, Greece. jparissis@yahoo.com <jparissis@yahoo.com>
Karavidas
Apostolos
A
Bistola
Vassiliki
V
Arapi
Sophia
S
Paraskevaidis
Ioannis A
IA
Farmakis
Dimitrios
D
Korres
Dimitrios
D
Filippatos
Gerasimos
G
Matsakas
Evaggelos
E
Kremastinos
Dimitrios T
DT
D000368:Aged; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D005996:Nitroglycerin / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage*; D012720:Severity of Illness Index; D000077464:Simendan; D012995:Solubility; D013318:Stroke Volume; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D006835:Hydrazones; D015850:Interleukin-6; D011724:Pyridazines; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D000077464:Simendan; D005996:Nitroglycerin