Papp Zoltán, Csapó Kálmán, Pollesello Piero, Haikala Heimo, Edes István
Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Medical and Health Science Center, Medical School, P.O. BOX 1, H-4004 Debrecen, Hungary.
Cardiovasc Drug Rev. 2005 Spring;23(1):71-98. doi: 10.1111/j.1527-3466.2005.tb00158.x.
Acute decompensation of chronic heart failure is a direct life-threatening situation with short-term mortality approaching 30%. A number of maladaptive changes are amplified within the cardiovascular system during the progression of chronic heart failure that makes the decompensation phase difficult to handle. Levosimendan is a new Ca2+-sensitizer for the treatment of acutely decompensated heart failure that has proved to be effective during the decompensation of chronic heart failure and acute myocardial infarction. Levosimendan differs from other cardiotonic agents that are used for acute heart failure in that it utilizes a unique dual mechanism of action: Ca2+-sensitization through binding to troponin C in the myocardium, and the opening of ATP-sensitive K+ channels in vascular smooth muscle. In general, these mechanisms evoke positive inotropy and vasodilation. Clinical studies suggested long-term benefits on mortality following short-term administration. It may, therefore, be inferred that levosimendan has additional effects on the cardiovascular system that are responsible for the prolongation of survival. Results of preclinical and clinical investigations suggest that the combination of levosimendan-induced cardiac and vascular changes has favorable effects on the coronary, pulmonary and peripheral circulations. Redistribution of the circulating blood offers an improved hemodynamic context for the development of a positive inotropic effect through Ca2+-sensitization of the contractile filaments, without a proportionate increase in myocardial oxygen consumption or the development of arrhythmias. Activation of ATP-sensitive K+ channels, both on sarcolemma and mitochondria, may protect against myocardial ischemia, and decreased levels of cytokines may prevent the development of further myocardial remodeling. Collectively, these effects of levosimendan shift the disturbed cardiovascular parameters towards normalization, thereby halting the perpetuation of the vicious cycle of heart failure progression. This may contribute to stabilization of the circulation and improved life expectancy of patients with chronic heart failure.
慢性心力衰竭急性失代偿是一种直接危及生命的情况，短期死亡率接近30%。在慢性心力衰竭进展过程中，心血管系统内会出现一些适应性不良变化，这使得失代偿期难以处理。左西孟旦是一种用于治疗急性失代偿性心力衰竭的新型钙增敏剂，已被证明在慢性心力衰竭失代偿和急性心肌梗死期间有效。左西孟旦与用于急性心力衰竭的其他强心剂不同，它采用独特的双重作用机制：通过与心肌肌钙蛋白C结合实现钙增敏，以及开放血管平滑肌中的ATP敏感性钾通道。一般来说，这些机制会引起正性肌力作用和血管舒张。临床研究表明短期给药对死亡率有长期益处。因此，可以推断左西孟旦对心血管系统有额外作用，这些作用有助于延长生存期。临床前和临床研究结果表明，左西孟旦引起的心脏和血管变化的组合对冠状动脉、肺循环和外周循环有有利影响。循环血液的重新分布为通过收缩细丝的钙增敏产生正性肌力作用提供了改善的血流动力学环境，而不会使心肌氧消耗成比例增加或发生心律失常。肌膜和线粒体上的ATP敏感性钾通道的激活可能预防心肌缺血，细胞因子水平的降低可能防止进一步的心肌重塑。总的来说，左西孟旦的这些作用使紊乱的心血管参数趋于正常化，从而阻止心力衰竭进展恶性循环的持续。这可能有助于稳定循环并提高慢性心力衰竭患者的预期寿命。
