Effects of levosimendan on left ventricular function: Correlation with plasma concentrations in conscious dogs

Abstract

Objectives : To test the hypothesis that the hemodynamic and left ventricular functional actions of levosimendan (Orion Pharmaceutical, Espoo, Finland), a new myofilament calcium sensitizer with phosphodiesterase-inhibiting properties, in conscious dogs are correlated with plasma concentrations of the drug measured with reverse-phase, high-performance liquid chromatography. Design : Prospective investiation. Setting : Research Laboratory. Participants : Fifteen chronically instrumented dogs. Interventions : On different experimental days, dogs were assigned to receive intravenous levosimendan (12 or 24 μg/kg loading dose and 0.2 or 0.4 μg/kg/min infusion, respectively). Measurements and Main Results : Systemic and coronary hemodynamics, left ventricular function, and plasma concentrations were determined at scheduled intervals during and after levosimendan infusions. Levosimendan increased heart rate and cardiac output and decreased left ventricular end-diastolic pressure and systemic vascular resistance. Levosimendan caused dose-related enhancement of left ventricular systolic (increases in regional preload recruitable stroke work slope and +dP dt max ) and diastolic functions (decreases in the time constant of isovolumic relaxation and regional chamber stiffness). The elimination half-life of levosimendan was 0.76 ± 0.04 hours. Conclusions : The hemodynamic actions and left ventricular functional effects of levosimendan correlated closely with plasma concentrations and returned to baseline values within 3 hours after discontinuation of the drug.