Effects of levosimendan in experimental acute coxsackievirus myocarditis

See Editorial on page 839. Abstract Background Acute heart failure is a potentially fatal manifestation of viral myocarditis. Development of myocardial damage in myocarditis involves cardiomyocyte apoptosis. Levosimendan is a novel calcium sensitizing inotropic agent with anti-apoptotic properties. We studied the feasibility of inotropic treatment with levosimendan and its effects on apoptosis in experimental acute heart failure caused by coxsackievirus myocarditis. Materials and methods Adolescent BALB/c mice were infected with myocarditic Woodruff variant of coxsackievirus B3 (2 x 104 plaque-forming units). Mice were randomized into those receiving levosimendan 0 center dot 33 mg kg-1 (total dose 1 mg kg-1 day-1) (n = 20) or vehicle (n = 19) given orally by gauge three times a day for 7 days after infection. Left ventricular function was evaluated by transthoracic echocardiography and the mice were euthanized on day 7. Histopathology, amount of virus in the heart (virus titration assay) and cardiomyocyte apoptosis (TUNEL assay) were studied. Uninfected untreated control mice were also studied. Results Infection resulted in histopathologically severe myocarditis and significant impairment of left ventricular function. Levosimendan treatment significantly improved ventricular function (fractional shortening 0 center dot 32 +/- 0 center dot 04 vs. 0 center dot 23 +/- 0 center dot 05, P = 0 center dot 005; contractility 0 center dot 60 +/- 0 center dot 12 vs. 0 center dot 39 +/- 0 center dot 14, P = 0 center dot 007 and myocardial performance index 0 center dot 36 +/- 0 center dot 06 vs. 0 center dot 62 +/- 0 center dot 15, P < 0 center dot 0001) compared with vehicle. Levosimendan also reduced cardiomyocyte apoptosis (0 center dot 26 +/- 0 center dot 08% vs. 0 center dot 44 +/- 0 center dot 15% in vehicle, P = 0 center dot 008), but did not have an effect on areas of myocardial necrosis or inflammation, or the amount of virus in the heart. Levosimendan treatment did not affect mortality (total mortality 63%). Conclusions Levosimendan improves ventricular function and inhibits cardiomyocyte apoptosis; therefore, it is suggested as a potentially feasible therapy in acute heart failure caused by viral myocarditis.