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首页> 外文期刊>Current medicinal chemistry. Cardiovascular and hematological agents >Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart.
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Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart.

机译:左西孟旦在失代偿性心力衰竭中的抗炎和抗凋亡作用:药物诱导的衰竭心脏收缩性能改善的新机制。

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摘要

Recent experimental and clinical observations indicate that over-expression of pro-inflammatory cytokines is actively implicated to chronic heart failure progression through their cytotoxic and negative inotropic effects. Calcium-sensitizing agents, such as levosimendan, promotes inotropy by stabilizing troponin C in a configuration that enhances the calcium sensitivity of cardiac myofilaments, preserving also diastolic relaxation. Levosimendan also opens ATP-dependent potassium channels in peripheral vessels, leading to vasodilatation. Large scale randomized clinical trials have shown that levosimendan administration in patients with severe heart failure due to left ventricular systolic dysfunction results in favorable hemodynamic changes, symptomatic benefit, and a reduction in short-term morbidity and mortality. This review describes current knowledge about novel cellular mechanisms associated with beneficial effects of levosimendan on cardiac contractile performance, focusing mainly on its immunomodulatory and anti-apoptotic properties. Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand. Modulation of pro-inflammatory and pro-apoptotic pathways into the failing heart by levosimendan may be an additional pathophysiologic mechanism that prevents further clinical and hemodynamic consequences of abnormal immune responses in decompensated heart failure and beneficially affects the progression of the syndrome.
机译:最近的实验和临床观察表明,促炎性细胞因子的过表达通过其细胞毒性和负性肌力作用积极地参与慢性心力衰竭的进展。钙增敏剂(如左西孟旦)通过稳定肌钙蛋白C的构型来增强肌力,这种构型可增强心肌细丝的钙敏感性,同时还可保持舒张期舒张。左西孟旦还在外周血管中打开ATP依赖性钾通道,导致血管舒张。大规模的随机临床试验表明,左心室收缩功能不全导致严重心力衰竭的患者应用左西孟旦可导致良好的血液动力学变化,对症治疗,并降低短期发病率和死亡率。这篇综述描述了与左西孟旦对心脏收缩性能的有益作用有关的新型细胞机制的当前知识,主要集中在其免疫调节和抗凋亡特性上。左西孟旦诱导的重度心力衰竭患者收缩储备和临床状况的改善似乎与主要促炎细胞因子(TNF-α,IL-6)和可溶性凋亡信号分子Fas / Fas配体的减少有关。左西孟旦调节促炎和促凋亡途径进入衰竭心脏可能是一种额外的病理生理机制,可防止失代偿性心衰中异常免疫反应的进一步临床和血液动力学后果,并有益地影响该综合征的进展。

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