Omecamtiv mecarbil (OM) is a putative positive inotropic tool for treatment of systolic heart dysfunction, based on the finding that in vivo it increases the ejection fraction and in vitro it prolongs the actin-bond life time of the cardiac and slow-skeletal muscle isoforms of myosin. OM action in situ, however, is still poorly understood as the enhanced Ca²⁺-sensitivity of the myofilaments is at odds with the reduction of force and rate of force development observed at saturating Ca²⁺. Here we show, by combining fast sarcomere-level mechanics and ATPase measurements in single slow demembranated fibres from rabbit soleus, that the depressant effect of OM on the force per attached motor is reversed, without effect on the ATPase rate, by physiological concentrations of inorganic phosphate (Pi) (1-10 mM). This mechanism could underpin an energetically efficient reduction of systolic tension cost in OM-treated patients, whenever [Pi] increases with heart-beat frequency.

Omecamtiv mecarbil（OM）是用于治疗收缩期心脏功能障碍的公认的正性正性肌力工具，基于以下发现：在体内它增加了射血分数，而在体外它延长了心肌和慢骨骼肌同种型的肌动蛋白键寿命。肌球蛋白。然而，由于肌丝的Ca ²⁺敏感性增强与饱和Ca ^2+时所观察到的力降低和力发展速率不一致，因此对OM原位作用仍知之甚少。在这里，我们通过结合快速的肌小节水平力学和ATP比酶测量兔比目鱼的单个缓慢脱膜纤维，通过无机物的生理浓度逆转了OM对每个附着运动力的抑制作用，而没有影响ATPase速率。磷酸盐（Pi）（1-10 mM）。每当Pi随心跳频率增加时，该机制可支持能量有效降低OM治疗患者的收缩压成本。