Cavusoglu Yuksel
Department of Cardiology, Faculty of Medicine, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
Expert Opin Pharmacother. 2007 Apr;8(5):665-77. doi: 10.1517/14656566.8.5.665.
Levosimendan is a new calcium sensitizer with inotropic and vasodilatory actions mediated by the sensitization of contractile proteins to calcium, opening of potassium channels and inhibition of phosphodiesterase-3. Its alternative mechanisms of action to those of other traditional inotropes provide a new approach in the management of decompensated heart failure. In contrast to dobutamine, levosimendan does not increase myocardial oxygen demand and, therefore, it is thought to have a lower potential to induce increases in myocardial ischemia and cardiac arrhythmias. The commonly used inotropic agent dobutamine increases myocardial contractility at the expense of increased myocardial oxygen consumption and, therefore, it can result in poor outcomes. Although dobutamine may also have favorable hemodynamic and symptomatic effects, levosimendan has been shown to be superior to dobutamine in increasing cardiac output and decreasing pulmonary capillary wedge pressure in patients with decompensated heart failure. In the presence of concomitant beta-blocker therapy, these favorable effects were present or even more pronounced during treatment with levosimendan, but not dobutamine. However, the mortality benefit of levosimendan observed in earlier trials has not been confirmed in recent, larger clinical trials. A distinct advantage of levosimendan over dobutamine is its prolonged hemodynamic effects, which last for up to 7-9 days. There are more data on the safety of levosimendan in ischemic patients than with any other inotropic drug and, therefore, levosimendan seems to be safe and effective in patients with ischemic heart disease when used at the recommended doses. Despite advances in heart failure therapy, many patients experience clinical deterioration, or do not respond to a single inotropic drug. Increasing evidence suggests the use of levosimendan in combination with dobutamine in patients with decompensated heart failure that is refractory to dobutamine alone.
左西孟旦是一种新型钙增敏剂,具有正性肌力和血管舒张作用,其作用机制是通过使收缩蛋白对钙敏感、开放钾通道以及抑制磷酸二酯酶-3来介导的。与其他传统正性肌力药物相比,其作用机制不同,为失代偿性心力衰竭的治疗提供了新方法。与多巴酚丁胺不同,左西孟旦不会增加心肌氧需求,因此,人们认为它诱发心肌缺血和心律失常增加的可能性较低。常用的正性肌力药物多巴酚丁胺以增加心肌氧消耗为代价来增加心肌收缩力,因此,可能导致不良后果。尽管多巴酚丁胺也可能具有有利的血流动力学和症状改善作用,但在失代偿性心力衰竭患者中,左西孟旦在增加心输出量和降低肺毛细血管楔压方面已被证明优于多巴酚丁胺。在联合使用β受体阻滞剂治疗的情况下,这些有利作用在左西孟旦治疗期间存在甚至更明显,但在多巴酚丁胺治疗期间则不然。然而,早期试验中观察到的左西孟旦的死亡率获益在最近更大规模的临床试验中尚未得到证实。左西孟旦相对于多巴酚丁胺的一个明显优势是其血流动力学作用持续时间较长,可持续长达7 - 9天。与任何其他正性肌力药物相比,关于左西孟旦在缺血性患者中的安全性的数据更多,因此,按推荐剂量使用时,左西孟旦在缺血性心脏病患者中似乎是安全有效的。尽管心力衰竭治疗取得了进展,但许多患者仍出现临床恶化,或对单一正性肌力药物无反应。越来越多的证据表明左西孟旦与多巴酚丁胺联合用于对单独使用多巴酚丁胺难治的失代偿性心力衰竭患者。