Levosimendan potentiates the inotropic actions of dopamine in conscious dogs.
We examined the hemodynamic and left ventricular (LV) functional actions of dopamine with and without levosimendan in dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dtmax, subendocardial segment length, and cardiac output (CO). On different experimental days, dogs were randomly assigned to receive dopamine (2.5, 5.0, and 10.0 micrograms kg-1 min-1) in the absence and presence of levosimendan (0.125, 0.25, and 0.5 microgram kg-1 min-1) or levosimendan alone. Dopamine increased heart rate (HR), CO, stroke volume (SV), and pressure-work index (PWI) and decreased systemic vascular resistance (SVR). Dopamine also increased LV systolic and end-diastolic pressures (LVSP and LVEDP) and mean arterial pressure (MAP). Dopamine caused dose-related positive inotropic [increases in preload recruitable stroke work (Mw) and + dP/ dtmax] and lusitropic effects [decreases in the time constant of isovolumic relaxation (tau) and increases in maximum segment-lengthening velocity (dL/dtmax)]. Dopamine also increased the regional chamber thickness constant (Kp) 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 the addition of levosimendan. Dopamine-induced increases in Mw and +dP/dtmax were enhanced by levosimendan. Reductions in tau and increases in dL/dtmax produced by dopamine were similar with and without levosimendan. However, levosimendan abolished increases in Kp caused by 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 dopamine in conscious, unsedated dogs, while attenuating the deleterious action of dopamine on chamber compliance.
McGough
M F
MF
Department of Medicine (Division of Cardiology), Medical College of Wisconsin, Milwaukee 53226, USA.
Pagel
P S
PS
Lowe
D
D
Hettrick
D A
DA
Warltier
D C
DC
D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013268:Stimulation, Chemical; D013997:Time Factors
D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan; D004298:Dopamine