Gheorghiade Mihai, Teerlink John R, Mebazaa Alexandre
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Am J Cardiol. 2005 Sep 19;96(6A):68G-73G. doi: 10.1016/j.amjcard.2005.07.023.
Current therapies for acute heart failure syndromes (AHFS) target hemodynamics by decreasing congestion or increasing myocardial contraction. Several new agents for AHFS use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and anti-stunning effects, blocking vasopressin receptors, or blocking endothelin-1 receptors. For example, levosimendan acts as a calcium sensitizer and adenosine triphosphate-dependent potassium (K(ATP)) channel opener that increases contraction, causes vasodilation, and provides cardioprotective effects. This is accomplished by its dual mechanism of action. Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels. Thus, contraction is increased with no significant increase in myocardial oxygen consumption. The opening of K(ATP) channels by levosimendan causes vasodilation and exerts anti-ischemic and anti-stunning effects on the myocardium. Other new agents target neurohormonal pathways. Tezosentan is an antagonist of endothelin-1 receptors A and B. By inhibiting endothelin-1 receptors, tezosentan may counteract the activities of endothelin-1, which include vasoconstriction, proarrhythmic activities, potentiation of other neurohormones, and mediation of increased vascular permeability. Tolvaptan is a vasopressin V2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss). Therefore, by using novel mechanisms of action, these agents may provide new opportunities for helping patients with AHFS.
目前用于急性心力衰竭综合征(AHFS)的治疗方法通过减轻充血或增强心肌收缩来针对血流动力学。几种用于AHFS的新型药物采用了新的作用机制,聚焦于新的治疗靶点,例如那些具有抗缺血和抗心肌顿抑作用、阻断血管加压素受体或阻断内皮素-1受体的靶点。例如,左西孟旦作为一种钙增敏剂和三磷酸腺苷依赖性钾(K(ATP))通道开放剂,可增强收缩、引起血管舒张并提供心脏保护作用。这是通过其双重作用机制实现的。左西孟旦与心肌肌钙蛋白C结合,从而增强钙细丝反应性并增加心肌收缩,而不增加细胞内钙水平。因此,收缩增强而心肌氧消耗无显著增加。左西孟旦开放K(ATP)通道可引起血管舒张,并对心肌发挥抗缺血和抗心肌顿抑作用。其他新型药物则针对神经激素途径。替唑生坦是内皮素-1受体A和B的拮抗剂。通过抑制内皮素-1受体,替唑生坦可能抵消内皮素-1的活性,内皮素-1的活性包括血管收缩、促心律失常作用、增强其他神经激素的作用以及介导血管通透性增加。托伐普坦是一种血管加压素V2受体拮抗剂,起利水剂的作用(即它增加尿量和血清钠,而钠丢失很少或无钠丢失)。因此,通过采用新的作用机制,这些药物可能为帮助AHFS患者提供新的机会。