Abstract
Omecamtiv mecarbil (OM) is a myosin activator agent developed for the treatment of heart failure. OM was reported to increase left ventricular ejection fraction and systolic ejection time, but little is known about the effect of heart rate on the action of OM. The present study, therefore, was designed to investigate the effects of OM on unloaded cell shortening and intracellular Ca2+ ([Ca2+]i) transients as a function of the pacing frequency. Isolated cardiomyocytes were stimulated at various frequencies under steady-state conditions. Cell length was monitored by an optical edge detector and changes in [Ca2+]i were followed using the Ca2+-sensitive dye Fura-2. At the pacing frequency of 1Hz, OM (1-10μM) significantly decreased both diastolic and systolic cell length, however, fractional shortening was augmented only by 1μM OM. Time to peak tension and time of 90% relaxation were progressively increased by OM. At the frequency of 2Hz, diastolic cell length was reduced by 10μM OM to a larger extent than systolic cell length, resulting in a significantly decreased fractional shortening under these conditions. OM had no effect on the parameters of the [Ca2+]i transient at any pacing frequency. The results suggest that supratherapeutic concentrations of OM may decrease rather than increase the force of cardiac contraction especially in tachycardic patients.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call