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)-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.

Levosimendan erken dönem sepsiste aortada “transforming growth factor beta” ve Smad iþaretlenmesini up-regüle eder

AMAÇ
Bu prospektif kontrollü deneysel çalýþma, levosimendanýn erken dönem sepsiste transforming growth factor (TGF)-β3 ve Smad1, Smad2 ve Smad3 oluþumuna etkilerini araþtýrmak amacýyla planlandý.
GEREÇ VE YÖNTEM
Yirmi dört sýçan rasgele dört gruba ayrýldý: 1) sham kontrol grubu 2) dobutamin grubu - abdominal hipertansiyon, çekal ligasyon ve delme (ÇLD) tekniði ile peritonit modeli prensibiyle sepsis oluþturuldu, sonra sýçanlar 10 µg.kg-1 dk-1 intravenöz (IV) dobutamin infüzyonu ile tedavi edildi, 3) levosimendan grubu - 2. grupta olduðu gibi sepsis modeli gerçekleþtirildi sonra sýçanlar levosimendan IV bolus 200 µg.kg-1 takiben, 200 µg.kg.-1 dk-1 IV infüzyonu ile tedavi edildi, 4) kontrol grubundakilere tedavi yapýlmadý. Tüm sýçanlar ÇLD’den 8 saat sonra öldürüldü. Aort doku örnekleri immünohistokimyasal olarak boyandý.
BULGULAR
ÇLD hem kontrol, hem de dobutamin gruplarýnda ýlýmlý IL-1 boyanmasýna neden oldu. Tumor necrosis factor (TNF)-α immünreaktivitesi sham ve kontrol grubunda ýlýmlýydý. Sham, kontrol ve dobutamin gruplarýnda TGF-β3 ýlýmlý derecede yüksek bulunurken, bu parametre levosmendan grubunda orta derecede yüksek saptandý. Smad1, Smad2 ve Smad3 levosmendan grubunda orta derecede yükselmiþ olarak saptandý.
SONUÇ
Levosimendanýn hemodinami ve global oksijen taþýnmasýna saðladýðý olumlu etkiler, deneysel ve klinik çalýþmalarda bildirilmiþtir. Levosimendanýn C++ iyon duyarlýlýðý üzerine etkileri yaný sýra, TGF-β3, Smad1, Smad2 ve Smad3 oluþumunu etkileyerek enflamasyonda sitokin salýnýmýna da etkileri olabilir.