Levosimendan pretreatment improves survival of septic rats after partial hepatectomy and suppresses iNOS induction in cytokine-stimulated hepatocytes

Abstract

Abstract We evaluated the survival effects and biochemical profiles of levosimendan in septic rats after partial hepatectomy and investigated its effects in cultured hepatocytes. Thirty-two rats underwent 70% hepatectomy and were randomised equally into four groups, followed by lipopolysaccharide (LPS) injection (250 µg/kg, i.v.) after 48 h. Levosimendan was given (i.p.) 1 h before LPS injection [group (A) levosimendan 2 mg/kg; (B) 1; (C) 0.5; (D) vehicle]. Survival at 7 days was increased significantly in group A compared with that in group D [A: 63%; B: 38%; C: 13%; D: 0%]. In serum, levosimendan decreased the level of tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and nitric oxide (NO). In remnant livers, levosimendan inhibited inducible nitric oxide synthase (iNOS) gene expression. In primary cultured rat hepatocytes stimulated by IL-1β, levosimendan suppressed NO production by inhibiting iNOS promoter activity and stability of its mRNA.