A dose-response study of levosimendan in a porcine model of acute ischaemic heart failure

作者：Kolseth Solveig Moss^*; Wahba Alexander; Kirkeby Garstad Idar; Aro Sakari; Nordgaard Havard; Hoydal Morten; Rognmo Oivind; Nordhaug Dag

来源：European Journal of Cardio-Thoracic Surgery, 2012, 41(6): 1377-1383.

DOI：10.1093/ejcts/ezr201

• Dose-response study
• Haemodynamics
• Inotropy
• Mechanoenergetics
• Mitochondrial respiration
• Phosphodiesterase inhibition

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. %26lt;br%26gt;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 mu g/kg, D2: 10 mu g/kg, D3: 40 mu g/kg, D4: 80 mu g/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. %26lt;br%26gt;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/dt(max) was slightly increased at dose 4 (P %26lt; 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. %26lt;br%26gt;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.

• 出版日期2012-6