Levosimendan up-regulates transforming growth factor-beta and smad signaling in the aorta in the early stage of sepsis; [Levosimendan erken dönem sepsiste aortada "transforming growth factor beta" ve Smad işaretlenmesini up-regüle eder]
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Date
2010
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Abstract
BACKGROUND This prospective, controlled experimental study was planned to investigate the effects of levosimendan on transforming growth factor (TGF)-β3 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 μg.kg-1min-1 intravenous (IV) dobutamine infusion, 3) levosimendan group - as in 2, then treated with levosimendan IV bolus 200 μg.kg-1 followed by 200 μg.kg.-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)-α was mild in both sham and control groups. TGF-β3 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. CONCLUSION 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-β3 and Smad1, Smad2 and Smad3 expression.
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Keywords
Animals , Aorta , Blood Pressure , Dopamine , Hydrazones , Male , Pyridazines , Rats , Rats, Wistar , Sepsis , Smad1 Protein , Smad2 Protein , Smad3 Protein , Transforming Growth Factor beta3 , Tumor Necrosis Factor-alpha , Vasodilator Agents , dobutamine , interleukin 1 , levosimendan , Smad protein , Smad1 protein , Smad2 protein , Smad3 protein , transforming growth factor beta , dopamine , hydrazone derivative , Madh2 protein, rat , Madh3 protein, rat , pyridazine derivative , simendan , Smad1 protein , Smad1 protein, rat , Smad2 protein , Smad3 protein , transforming growth factor beta3 , tumor necrosis factor alpha , vasodilator agent , aorta , article , controlled study , drug effect , immunohistochemistry , immunoreactivity , nonhuman , rat , sepsis , animal , blood pressure , drug effects , genetics , male , pathophysiology , physiology , sepsis , Wistar rat