Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects.

AimsThe aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocardial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting. Methods and ResultsTwenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n=8), 8 (n=8) or 24 (n=7) g . kg 1 of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats . min 1 after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6 l . min 1 (P<0·05 for both) after 8 and 24 g . kg 1 of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42 ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly.Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen consumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.

Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.

Dynamic positron emission tomography (PET) with [11C]acetate allows noninvasive assessment of myocardial oxygen consumption. In combination with echocardiography, PET enables determination of cardiac efficiency (defined as useful cardiac work per unit of oxygen consumption). We used this approach to compare the effects of levosimendan, a Ca(2+)-dependent calcium sensitizer, with dobutamine and sodium nitroprusside in healthy male volunteers. The effects of levosimendan on k(mono), an index of oxygen consumption, and cardiac efficiency were neutral, whereas the hemodynamic profile was consistent with balanced inotropism and vasodilatation. Dobutamine enhanced cardiac efficiency at the expense of increased oxygen requirement, but the effects of nitroprusside on k(mono) and cardiac efficiency were neutral. This study shows the feasibility of PET in phase 1 pharmacodynamic studies and suggests potential energetical advantages of calcium sensitization with levosimendan.