Toller Wolfgang G, Stranz Christian
Department of Anesthesiology and Intensive Care Medicine, Medical University Graz, Austria.
Anesthesiology. 2006 Mar;104(3):556-69. doi: 10.1097/00000542-200603000-00024.
Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.
多项临床研究表明,包括β1肾上腺素能受体激动剂和磷酸二酯酶III抑制剂在内的现有正性肌力药物在心力衰竭的短期和长期治疗中存在重大局限性。这些有害作用的原因与这些药物的作用机制有关,包括细胞内Ca2+增加,随后心肌需氧量增加和心律失常的发生。左西孟旦是一种具有正性肌力作用的肌丝Ca2+增敏剂,可增加心肌性能,而氧耗无显著变化,对心律呈中性影响。此外,左西孟旦具有血管舒张作用,这是通过刺激三磷酸腺苷依赖性钾通道实现的。这种作用在心肌缺血的情况下可能具有特殊意义。迄今为止,左西孟旦在全球31个国家获得批准,参与左西孟旦随机对照试验的心力衰竭患者比参与任何其他静脉注射正性肌力药物试验的患者更多。