Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure

OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fifteen anesthetized dogs. INTERVENTIONS: Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 μg/kg/min or levosimendan 12 μg/kg for 10 mins followed by 0.1 and 0.2 μg/kg/min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 ± 0.07 to 3.01 ± 0.28 mm Hg/mL, decreased Ees from 1.17 ± 0.09 to 0.58 ± 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 ± 0.09 to 0.22 ± 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects. © 2006 Lippincott Williams & Wilkins, Inc.