Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. Significant (p < 0.05) increases in heart rate (HR) and decreases in systemic vascular resistance (SVR) occurred 15 min after CPB in patients receiving placebo. Later increases in mean arterial pressure (MAP) and cardiac output (CO) and decreases in stroke volume (SV) and pulmonary vascular resistance also were observed. HR was greater in patients receiving high- but not low-dose levosimendan versus placebo immediately after CPB. MAP also was lower in patients treated with either dose of levosimendan compared with placebo after CPB. Levosimendan increased CO and decreased SVR (4.2 +/- 0.4 to 7.9 +/- 0.4 L/min and 1,150 +/- 99 to 512 +/- 42 dyn/s/cm5, respectively, 15 min after CPB; mean +/- SEM). CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.

The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycerin. Four groups consisting of 32 experiments were performed in 17 conscious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt_max, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded during control conditions and after intravenous administration of pirsidomine (1.0, 2.0, and 4.0 mg·kg^–1), SIN-1, (50, 100, and 200 µg·kg^–1), nitroprusside (0.5, 1.0, and 2.0 µg·kg^–1·min^–1), or nitroglycerin (1.0, 2.0, and 4.0 µg·kg^–1 • min^–1). Pirsidomine decreased mean arterial, left ventricular systolic and end-diastolic pressures, stroke volume and systemic vascular resistance. Diastolic coronary blood flow velocity and heart rate were increased and coronary vascular resistance decreased by pirsidomine. SIN-1, nitroprusside and nitroglycerin caused similar decreases in preload (evaluated by left ventricular end-diastolic pressure) and afterload (indirectly assessed by mean arterial pressure and systemic vascular resistance) as compared to pirsidomine. However, equihypotensive doses of SIN-1, nitroprusside, and nitroglycerin improved ventricular performance as assessed by increases in left ventricular dP/dt_max, cardiac output and segment shortening, in contrast to those findings during comparable doses of pirsidomine (4 mg·kg^–1)·Despite similar loading conditions, high doses of pirsidomine did not enhance left ventricular function, suggesting that pirsidomine may have direct negative inotropic effects.

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