Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.

ABSTRACT: Omecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. The effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment (Pdf), and a slowed rate of XB detachment (krel) at submaximal Ca2+ activations. Ca2+ sensitivity of force generation (pCa50) was higher in HF myocardium when compared with donor myocardium, both prior to and after OM incubations. OM incubation (0

SUBMITTER: Mamidi R 

PROVIDER: S-EPMC5685665 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature