Effects of omecamtiv mecarbil on failing human ventricular trabeculae and interaction with (−)-noradrenaline

Abstract

Omecamtiv mecarbil (OM) is a novel medicine for systolic heart failure, targeting myosin to enhance cardiomyocyte performance. To assist translation to clinical practice we investigated OMs effect on explanted human failing hearts, specifically; contractile dynamics, interaction with the β1–adrenoceptor (AR) agonist (−)-noradrenaline and spontaneous contractions. Left and right ventricular trabeculae from 13 explanted failing hearts, and trabeculae from 58 right atrial appendages of non-failing hearts, were incubated with or without a single concentration of OM for 120 min. Time to peak force (TPF) and 50% relaxation (t50%) were recorded. In other experiments, trabeculae were observed for spontaneous contractions and cumulative concentration-effect curves were established to (−)-noradrenaline at β1-ARs in the absence or presence of OM. OM prolonged TPF and t50% in ventricular trabeculae (600 nM, 2 µM, p