Ng T M H, Akhter M W
Department of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA.
Minerva Cardioangiol. 2005 Dec;53(6):565-84.
Levosimendan is a novel compound recently approved for the management of acute heart failure in Sweden and several European countries. Levosimendan exerts dual mechanisms of action associated with dose-dependent increases in cardiac output and decreases in pulmonary capillary wedge pressures. A positive inotropic effect is achieved through calcium sensitization, an effect of levosimendan binding to troponin C in a calcium-dependent manner. This mode of enhanced contractile force generation is achieved without an increase in myocardial oxygen consumption, intracellular calcium concentrations, or an adverse effect on diastolic function. The vasodilatory effect observed in cardiac, pulmonary and systemic vasculature occurs as a result of K-ATP channel activation, a mechanism which may also confer anti-ischemic properties. It remains unclear whether calcium sensitization or K-ATP channel activation is of greater clinical significance. Clinical studies utilizing fixed-dose infusions of 6 to 24 h in patients with left ventricular systolic dysfunction demonstrate greater safety and hemodynamic efficacy than placebo or dobutamine. This has translated into improved comparative survival at 31 days and potentially 180 days. Two additional prospective, outcome studies are being completed to confirm the beneficial effect on morbidity and mortality. Hypo-tension and decreased hematologic indices are the most common adverse effects requiring monitoring. No relevant drug interactions have been noted with chronic oral heart failure medications. Levosimendan's unique safety and efficacy profile suggests it is a rationale alternative to conventional inotropes, and potentially a useful first line agent for management of acute decompensated heart failure. Its role in other clinical scenarios, such as for cardiac surgery, diastolic dysfunction and outpatient infusion therapy, continues to evolve.
左西孟旦是一种新型化合物，最近在瑞典和几个欧洲国家被批准用于治疗急性心力衰竭。左西孟旦具有双重作用机制，与心输出量剂量依赖性增加和肺毛细血管楔压降低相关。通过钙增敏作用实现正性肌力作用，即左西孟旦以钙依赖方式与肌钙蛋白C结合的效应。这种增强收缩力产生的方式在不增加心肌氧消耗、细胞内钙浓度或对舒张功能产生不良影响的情况下实现。在心脏、肺和全身血管系统中观察到的血管舒张作用是由于K-ATP通道激活所致，该机制也可能具有抗缺血特性。目前尚不清楚钙增敏作用或K-ATP通道激活在临床上哪个更具重要意义。对左心室收缩功能障碍患者进行6至24小时固定剂量输注的临床研究表明，与安慰剂或多巴酚丁胺相比，其安全性和血流动力学疗效更佳。这已转化为31天及可能180天时更好的相对生存率。另外两项前瞻性结局研究正在完成，以证实其对发病率和死亡率的有益影响。低血压和血液学指标下降是最常见的需要监测的不良反应。未发现与慢性口服心力衰竭药物有相关药物相互作用。左西孟旦独特的安全性和疗效表明，它是传统强心剂的合理替代药物，可能是治疗急性失代偿性心力衰竭的有用一线药物。其在其他临床场景中的作用，如心脏手术、舒张功能障碍和门诊输注治疗，仍在不断演变。
