Preconditioning With Levosimendan Prevents Contractile Dysfunction Due To H2O2-induced Oxidative Stress in Human Myocardium

Abstract

We studied the inotropic and possible antioxidant effects of levosimendan in human atrial strips, before and after induction of oxidative stress induced by H2O2. Levosimendan (10(-9) to 10(-6) M) increased contractions induced by electrical stimulation (ES) in human atrial strips. The maximal positive inotropic effect of levosimendan was 145.6 +/- 4.6% of predrug values. H2O2 (10(-6) to 10(-3) M) significantly reduced contractions induced by ES. The maximum inhibition by H2O2 on the ES induced contraction was 47.2 +/- 3.5%. Levosimendan significantly increased the isometric contractions induced by ES when compared with the values obtained in the presence of 10 M H2O2 by 89.0 +/- 4.7%, 98.9 +/- 3.4%, and 111.2 +/- 3.7% at 10(-8), 10(-7), and 10(-6) M concentrations, respectively. In concentrations of 10(-7) and 10(-6) M levosimendan, the maximum responses to ES increased when compared with the values obtained in the presence of 10(-3) M H2O2 by 87.1 +/- 3.6% and 95.1 +/- 5.3%, respectively. The cumulatively applied H2O2 (10(-6)-10(-3) M) did not change the positive inotropic response to levosimendan. In conclusion, levosimendan reverses the myocardial dysfunction induced by oxidative stress in human right atrial strips. Levosimendan prevents myocardial dysfunction if administered before oxidative stress.