EFFECTS OF LEVOSIMENDAN ON LEFT-VENTRICULAR FUNCTION - CORRELATION WITH PLASMA-CONCENTRATIONS IN CONSCIOUS DOGS

Objectives: To test the hypothesis that the hemodynamic and left ventr icular functional actions of levosimendan (Orion Pharmaceutica, Espoo, Finland), a new myofilament calcium sensitizer with phosphodiesterase -inhibiting properties, in conscious dogs are correlated with plasma c oncentrations of the drug measured with reverse-phase, highperformance liquid chromatography. Design: Prospective investigation. Setting: Re search laboratory. Participants: Fifteen chronically instrumented dogs . Interventions: On different experimental days, dogs were assigned to receive intravenous levosimendan (12 or 24 mu g/kg loading dose and 0 .2 or 0.4 mu g/kg/min infusion, respectively). Measurements and Main R esults: Systemic and coronary hemodynamics, left ventricular function, and plasma concentrations were determined at scheduled intervals duri ng and after levosimendan infusions. Levosimendan increased heart rate and cardiac output and decreased left ventricular end-diastolic press ure and systemic vascular resistance. Levosimendan caused dose-related enhancement of left ventricular systolic (increases in regional prelo ad recruitable stroke work slope and +dP/dt(max)) and diastolic functi ons (decreases in the time constant of isovolumic relaxation and regio nal chamber stiffness). The elimination half-life of levosimendan was 0.76 +/- 0.04 hours. Conclusions: The hemodynamic actions and left ven tricular functional effects of levosimendan correlated closely with pl asma concentrations and returned to baseline values within 3 hours aft er discontinuation of the drug. Copyright (C) 1997 by W.B. Saunders Co mpany.