Levosimendan up-regulates transforming growth factor-beta and Smad signaling in the aorta in the early stage of sepsis
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BACKGROUND This prospective, controlled experimental study was planned to investigate the effects of levosimendan on transforming growth factor (TGF)-beta 3 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 mu g.kg(-1)min(-1) intravenous (IV) dobutamine infusion, 3) levosimendan group - as in 2, then treated with levosimendan IV bolus 200 mu g.kg(-1) followed by 200 mu g.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)-alpha was mild in both sham and control groups. TGF-beta 3 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-beta 3 and Smad1, Smad2 and Smad3 expression.