Thorac Cardiovasc Surg 2015; 63 - ePP93
DOI: 10.1055/s-0035-1544589

Levosimendan Protect Human Hepatocytes from Ischemia/Reperfusion Injury: A Second Benefit for Patients with Acute Heart Failure?

I. Werner 1, S. Brunner 1, P. Meybohm 2, A. Moritz 1, U. A. Stock 1, A. Beiras-Fernandez 1
  • 1Universitätsklinikum Frankfurt, Goethe Universität, Thorax-, Herz-, Thorakale Gefäßchirurgie, Frankfurt am Main, Germany
  • 2Universitätsklinikum Frankfurt, Goethe Universität, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Frankfurt am Main, Germany

Objective: Levosimendan is an inotropic agent used in the management of acute heart failure. Levosimendan increases calcium sensitivity of the myocardial contractile elements, as well as shows vasodilatatory effects by opening ATP-sensitive potassium channels in vascular smooth muscle cells. Patients in acute heart failure present often with liver damage due to transient ischemia. Recent animal studies provided first evidence about an anti-ischemic effect of levosimendan after ischemia/reperfusion (I/R) injury, suggesting a direct cellular protective effect. Thus, we investigated the dose and time dependent effect of levosimendan on human hepatocytes after I/R injury.

Methods: Human hepatocytes were either exposed to I/R injury or remained under normoxic conditions previous to drug treatment. The hepatocytes were then treated with 10ng/ml, 100ng/ml or 1000ng/ml of levosimendan for 24h and 48h. Cell viability was measured via an MTT assay. Untreated hepatocytes served as controls and cells treated with saponin served as positive control. Oxidative stress and hepatocyte damage was evaluated via monitoring lipid peroxidation and AST enzyme activity.

Results: Levosimendan treatment for 24h after I/R injury showed to act protective on hepatocytes. This effect was dose dependent, whereas the protective effect was constantly high after 48h and no difference in dosage was detectable. Besides cell viability a reduction in AST enzyme activity, an indicator of liver damage, was shown in a time dependent manner comparing 24h and 48h. High dosage and long term treatment significantly reduced the damage on hepatocytes.

Conclusion: Levosimendan treatment after I/R injury seems to positively influence hepatocyte viability. Furthermore we could show that levosimendan is able to alter AST enzyme activity and oxidative stress in our experimental set-up. In case of I/R injury, as shown by patients with acute heart failure, levosimendan may also provide an treatment option to preserve liver function, independently of the inotropic benefit.