Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology, Trondheim, Norway.
Eur J Cardiothorac Surg. 2012 Jun;41(6):1377-83. doi: 10.1093/ejcts/ezr201. Epub 2011 Dec 23.
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.
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.
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 < 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.
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.
左西孟旦是一种新型正性肌力药物，据称通过钙离子增敏作用改善心肌收缩力。我们的目的是评估左西孟旦在急性缺血性心力衰竭猪模型中的剂量依赖性对左心室（LV）收缩力和能量特性的影响。
在麻醉开胸的体内动物模型中使用了 6 头猪。测量的时间点为：基线、心力衰竭诱导后和剂量 1-4（D1-D4）后。在左冠状动脉微栓塞之前输注四种不同剂量（D1：2.5μg/kg，D2：10μg/kg，D3：40μg/kg，D4：80μg/kg）的左西孟旦后，诱导心力衰竭。通过压力-导纳导管技术评估血液动力学。根据冠状动脉流量测量值和冠状动脉窦血气计算 LV 耗氧量。研究了 LV 活检中的线粒体呼吸。
左西孟旦对收缩力没有显著的、不依赖于负荷的影响（负荷可诱导的收缩功斜率在心力衰竭后即刻为 34mmHg，而在 D1-D4 时分别为 39（P=0.406）、42（P=0.219）、46（P=0.067）和 41（P=0.267）），尽管更依赖于负荷的收缩性指标 dP/dt(max) 在剂量 4 时略有增加（P<0.05）。在所有剂量下，LV 能量转换效率（PVA-MVO2 关系）保持不变。在心力衰竭诱导后，最大线粒体呼吸降低，并且在左西孟旦输注期间仍保持不变的低水平。
令人惊讶的是，在急性心力衰竭的猪模型中，左西孟旦对 LV 的收缩力、能量效率和线粒体呼吸没有显著影响。在高剂量下，左西孟旦引起血管扩张并增加心率和心输出量。
