Abstract
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.
Publication types
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Clinical Trial
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Controlled Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Calcium / metabolism*
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Carbon Radioisotopes
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Cardiotonic Agents / administration & dosage
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Cardiotonic Agents / pharmacology*
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Chromatography, High Pressure Liquid
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Dobutamine / administration & dosage
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Dobutamine / pharmacology
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Echocardiography
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Epinephrine / blood
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Feasibility Studies
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Heart / drug effects*
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Hemodynamics / drug effects
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Humans
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Hydrazones / administration & dosage
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Hydrazones / pharmacology*
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Male
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Myocardial Contraction / drug effects
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Myocardium / metabolism*
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Nitroprusside / administration & dosage
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Nitroprusside / pharmacology
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Norepinephrine / blood
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Oxygen Consumption / drug effects
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Pyridazines / administration & dosage
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Pyridazines / pharmacology*
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Simendan
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Sympathomimetics / administration & dosage
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Sympathomimetics / pharmacology
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Tomography, Emission-Computed
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Vasodilation / drug effects
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Vasodilator Agents / administration & dosage
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Vasodilator Agents / pharmacology
Substances
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Carbon Radioisotopes
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Cardiotonic Agents
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Hydrazones
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Pyridazines
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Sympathomimetics
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Vasodilator Agents
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Nitroprusside
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Simendan
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Dobutamine
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Calcium
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Norepinephrine
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Epinephrine