Determination of biological availability, time-to-peak and elimination half-life of inhaled levosimendan by administration of an inhaled- and intravenous dose of levosimendan.

Inclusion Criteria:

• Subject >18 years of age
• Scheduled for elective coronary artery bypass grafting (CABG)
• Provided written informed consent
• Impaired left ventricular function (LVEF <40%)

Exclusion Criteria:

• Known allergy for levosimendan or solutes
• Persistent angina, defined as Canadian Cardiovascular Society score > I
• History of valvular intervention or uncorrected primary stenotic valve disease
• Uncorrected thyroid disease
• Infiltrative, hypertrophic or restrictive cardiomyopathy
• Pericardial disease
• Active myocarditis
• Chronic obstructive pulmonary disease requiring long-term treatment with β-agonists, Theophylline, or corticosteroids (FEV1 < 80%; Tiffeneau-index <0.7)
• History of serious arrhythmias, defined as a history of ventricular tachycardia or fibrillation other than that occurring within 24 hours after acute myocardial infarction (MI)
• resting heart rate > 115 bpm for at least 10 minutes on repeated measurements
• Supine systolic blood pressure < 85 mm Hg or >200 mm Hg
• patients with implanted pacemaker/defibrillator or cardiac resynchronisation therapy (CRT-device)
• primary renal or hepatic impairment (creatinine > 2.5 mg/dL or aspartate aminotransferase/alanine aminotransferase >2 times upper limit of normal and/or increased level of bilirubin (> 2 times the upper limit of normal and increase of international normalised ratio (INR) above the upper limit of normal, respectively)
• Uncorrected hypokalemia or hyperkalemia (potassium <3.5 mmol/L or >5.5 mmol/L)
• Uncorrected hypomagnesemia (magnesium <0.65mmol/L)
• Treatment with another investigational agent within 30 days before study entry
• Intubated and mechanically ventilated at the time of study entry