Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure.
BACKGROUND
The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown.


OBJECTIVE
To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure.


METHODS
Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double-blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion.


RESULTS
Seven patients (1 levosimendan, 6 placebo), were excluded during follow-up. In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion. Serum sTNF-R2 was decreased at 24 h (p<0.05 vs baseline) and remained lower than baseline for at least 7 d (p<0.05).


CONCLUSIONS
These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-alpha receptors and sFAS, immediately after infusion, an effect which persists for 7-30 d.
Trikas
Athanasios
A
Athens University Medical School, A' Cardiology Department, Athens, Greece. atrikas@otenet.gr
Antoniades
Charalambos
C
Latsios
Giorgos
G
Vasiliadou
Karmen
K
Karamitros
Ioannis
I
Tousoulis
Dimitris
D
Tentolouris
Costantinos
C
Stefanadis
Christodoulos
C
D000368:Aged; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007263:Infusions, Parenteral; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D000077464:Simendan; D012995:Solubility; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019014:fas Receptor / Q000378:metabolism*
D006835:Hydrazones; D015850:Interleukin-6; D011724:Pyridazines; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000077464:Simendan