A novel myosin activator, omecamtiv mecarbil (OM), is a cardiac inotropic agent 
with a unique new mechanism of action, which is thought to arise from an 
increase in the transition rate of myosin into the actin-bound force-generating 
state without increasing calcium (Ca2+) transient. There remains, however, 
considerable controversy about the effects of OM on cardiac contractility and 
energy expenditure. In the present study, we investigated the effects of OM on 
left ventricular (LV) mechanical work and energetics, i.e., mechanoenergetics in 
rat normal hearts (CTL) and failing hearts induced by chronic administration of 
isoproterenol (1.2 mg/kg/day) for 4 weeks (ISO-HF). We analyzed the LV 
end-systolic pressure-volume relation (ESPVR) and the linear relation between 
the myocardial oxygen consumption per beat (VO2) and systolic pressure-volume 
area (PVA; a total mechanical energy per beat) in isovolumically contracting rat 
hearts at 240- or 300-bpm pacing in the absence or presence of OM. OM did not 
change the ESPVR in CTL and ISO-HF. OM, however, significantly decreased the 
slope of VO2-PVA relationship in both CTL and ISO-HF, and significantly 
increased the mean VO2 intercept without changes in basal metabolism in ISO-HF. 
These results suggested that OM improved the oxygen cost of PVA (contractile 
efficiency) with the unchanged LV contractility in both CTL and ISO-HF but 
increased VO2 for Ca2+ handling in excitation-contraction (E-C) coupling in 
ISO-HF. We concluded that OM improves contractile efficiency in normal and 
failing hearts but increases O2 consumption of Ca2+ handling in failing hearts 
in isovolumically contracting rat model.