LEVOSIMENDAN POTENTIATES THE INOTROPIC ACTIONS OF DOPAMINE IN CONSCIOUS DOGS

Vile examined the hemodynamic and left ventricular (LV) functional act ions of dopamine with and without levosimendan in dogs chronically ins trumented for measurement of aortic and LV pressure, +dP/dt(max), sube ndocardial segment length, and cardiac output (CO). On different exper imental days, dogs were randomly assigned to receive dopamine (2.5, 5. 0, and 10.0 mu g kg(-1) min(-1)) in the absence and presence of levosi mendan (0.125, 0.25, and 0.5 mu g kg(-1) min(-1)) or levosimendan alon e. Dopamine increased heart rate (HR), CO, stroke volume (SV), and pre ssure-work index (PWI) and decreased systemic vascular resistance (SVR ). Dopamine also increased LV systolic and end-diastolic pressures (LV SP and LVEDP) and mean arterial pressure (MAP). Dopamine caused dose-r elated positive inotropic [increases in preload recruitable stroke wor k (M(w)) and +dP/dt(max)] and lusitropic effects [decreases in the tim e constant of isovolumic relaxation (tau) and increases in maximum seg ment-lengthening velocity (dL/dt(max))]. Dopamine also increased the r egional chamber thickness constant (K-p) concomitant with increases in LVEDP. In the presence of levosimendan. dopamine-induced increases in HR, PWI, CO, and SV and decreases in SVR were enhanced. Increases in MAP, LVSP, and LVEDP observed with dopamine alone were attenuated by t he addition of levosimendan. Dopamine-induced increases in M(w) and +d P/dt(max) were enhanced by levosimendan. Reductions in tau and increas es in dL/dt(max) produced by dopamine we re similar with and without l evosimendan. However, levosimendan abolished increases in K-p caused b y dopamine alone. Levosimendan alone caused dose-related improvements in indices of LV systolic and diastolic function. The results indicate that levosimendan potentiates the positive inotropic effects of dopam ine in conscious, unsedated dogs, while attenuating the deleterious ac tion of dopamine on chamber compliance.