Objective: Experimental data suggest that levosimendan has pulmonary vasodilatory properties which, in combination with its positive inotropic effects, would render it particularly attractive for the treatment of right ventricular dysfunction. To test this hypothesis, we developed an experimental model of right ventricular failure and analyzed the effects of levosimendan on ventriculovascular coupling between the right ventricle and pulmonary artery (PA).
Design: Prospective, randomized, placebo-controlled animal study.
Setting: University hospital laboratory.
Subjects: Fourteen pigs (mean weight 36 ± 1 kg).
Interventions: Pigs were instrumented with biventricular conductance catheters, a PA and right coronary artery flow probe, and a high-fidelity pulmonary pressure catheter. Right ventricular dysfunction was induced by repetitive episodes of ischemia/reperfusion in the presence of temporary PA constriction. Pigs were randomly assigned to receive levosimendan (120 μg·kg−1·min−1 for 10 mins followed by continuous infusion of 60 μg·kg−1·min−1 for 45 mins) or the placebo (control).
Measurements and Main Results: Induction of right ventricular dysfunction resulted in a 42% decrease in contractility (reduction in slope of preload recruitable stroke work [Mw] from 2.5 ± 0.4 to 1.8 ± 0.5 mW·sec·mL−1; p = .02) and a 60% increase in right ventricular afterload (effective pulmonary arterial elastance [PA-Ea] from 0.6 ± 0.1 to 1.0 ± 0.3 mm Hg·mL−1; p < .01). Right ventriculovascular coupling, as assessed by the quotient of right ventricular end-systolic elastance (Emax) over PA-Ea, decreased from 1.23 ± 0.38 to 0.64 ± 0.21 (p = .03). Treatment with levosimendan improved right ventricular contractility (Mw from 1.9 ± 0.4 to 2.9 ± 0.5 mW·sec·mL−1; p < .01), lowered right ventricular afterload (PA-Ea from 1.1 ± 0.3 to 0.8 ± 0.3 mm Hg·mL−1; p = .02), and restored right ventriculovascular coupling to normal values (Emax/PA-Ea = 1.54 ± 0.51). Levosimendan also significantly increased coronary blood flow and left ventricular contractility (Mw from 7.2 ± 3.3 to 9.5 ± 2.9 mW·sec·mL−1; p = .01) but did not affect biventricular diastolic function.
Conclusions: In an experimental model of acute right ventricular dysfunction, levosimendan improved global hemodynamics and optimized right ventriculovascular coupling via a moderate increase in right ventricular contractility and a mild reduction of right ventricular afterload.