Levosimendan up-regulates transforming growth factor-beta and smad signaling in the aorta in the early stage of sepsis.
BACKGROUND
This prospective, controlled experimental study was planned to investigate the effects of levosimendan on transforming growth factor (TGF)-beta3 and Smad1, Smad2 and Smad3 expression in the early stages of sepsis.


METHODS
Twenty-four rats were randomized into four groups: (1) sham-operated controls, (2) dobutamine group--subjected to abdominal hypertension and peritonitis-induced sepsis using cecal ligation and puncture (CLP), then treated with 10 microg x kg(-1) min(-1) intravenous (IV) dobutamine infusion, (3) levosimendan group--as in 2, then treated with levosimendan IV bolus 200 microg x kg(-1) followed by 200 microg x kq(-1) min(-1) IV infusion, and (4) a control group as in 2, with no treatment. All rats were killed 8 hours after CLP. Aorta tissue samples were analyzed by immunohistochemical staining.


RESULTS
CLP caused mild interleukin (IL)-1 immunostaining in both control and dobutamine groups. Immunoreactivity of tumor necrosis factor (TNF)-alpha was mild in both sham and control groups. TGF-beta3 immunostaining was mildly increased in groups sham, control and dobutamine, whereas it was found moderate in group levosimendan. Smad1, Smad2 and Smad3 were found moderately increased only in group levosimendan.


CONCLUSIONS
Beneficial effects of levosimendan on hemodynamics and global oxygen transport were reported in experimental and clinical trials. Besides its potency on C++ ion sensitivity, it should influence inflammatory cytokine production by diminishing TGF-beta3 and Smad1, Smad2 and Smad3 expression.
Erbüyün
Koray
K
Department of Anesthesiology, Celal Bayar University, Faculty of Medicine, Manisa, Turkey. korayerbuyun@yahoo.com
Tok
Demet
D
Vatansever
Seda
S
Ok
Gülay
G
Türköz
Elgin
E
Aydede
Hasan
H
Erhan
Yamay
Y
Tekin
Idil
I
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000235:genetics / Q000503:physiopathology*; D000077464:Simendan; D051898:Smad1 Protein / Q000187:drug effects / Q000235:genetics; D051899:Smad2 Protein / Q000187:drug effects / Q000235:genetics; D051900:Smad3 Protein / Q000187:drug effects / Q000235:genetics; D053782:Transforming Growth Factor beta3 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology
D006835:Hydrazones; D011724:Pyridazines; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053782:Transforming Growth Factor beta3; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D000077464:Simendan; D004298:Dopamine