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  • Title: Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure.
    Author: Kerbaul F, Gariboldi V, Giorgi R, Mekkaoui C, Guieu R, Fesler P, Gouin F, Brimioulle S, Collart F.
    Journal: Crit Care Med; 2007 Aug; 35(8):1948-54. PubMed ID: 17568324.
    Abstract:
    OBJECTIVE: Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fourteen anesthetized piglets. INTERVENTIONS: Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline. MEASUREMENTS AND MAIN RESULTS: Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. CONCLUSIONS: A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.
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