A dose–response study of levosimendan in a porcine model of acute ischaemic heart failure
| Autor: | Solveig Moss Kolseth, Idar Kirkeby-Garstad, Øivind Rognmo, Dag Nordhaug, Morten A. Høydal, Sakari Aro, Håvard Nordgaard, Alexander Wahba |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pulmonary and Respiratory Medicine
Inotrope medicine.medical_specialty Cardiac output Cardiotonic Agents Sus scrofa Hemodynamics Mitochondria Heart Ventricular Function Left Contractility Oxygen Consumption Internal medicine Animals Medicine Simendan Coronary sinus Heart Failure Dose-Response Relationship Drug business.industry Hydrazones General Medicine Levosimendan medicine.disease Myocardial Contraction Pyridazines Disease Models Animal Preload Anesthesia Heart failure Cardiology Female Surgery Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | European Journal of Cardio-Thoracic Surgery. 41:1377-1383 |
| ISSN: | 1873-734X 1010-7940 |
| Popis: | OBJECTIVES: Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. METHODS: Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1–4 (D1–D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. RESULTS: Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P= 0.219), 46 (P = 0.067) and 41 (P= 0.267) at D1–D4), although the more load-dependent contractility indicator of dP/dtmax was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA–MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. CONCLUSIONS: Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output. |
| Databáze: | OpenAIRE |
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