Single cardiac myocytes from the left and right ventricles respond similarly to isoproterenol and omecamtiv mecarbil

Abstract

The left and right cardiac ventricles develop from different embryonic structures and generate different systolic pressures in vivo (left ventricle ~120 mm Hg, right ventricle, ~25 mm Hg). Some patients also develop chamber‐specific hypertrophy. We measured the contractile properties of cells isolated from the left and right ventricles of rat hearts and tested how they responded to omecamtiv mecarbil and isoproterenol. Based on data from ongoing experiments using human samples in our laboratory, our hypothesis was that cells from the left and right ventricles would exhibit similar contractile effects. Cells were isolated from 3 to 6 month old female Sprague Dawley rats by enzymatic digestion. Shortening profiles and calcium transients were measured at 32°C using video microscopy and Fura2‐AM fluorescence respectively. Statistical tests were performed using linear mixed models. A total of ~150 cells were analyzed using isoproterenol concentrations ranging from 0 to 1.0 μM and omecamtiv mecarbil concentrations ranging from 0 to 10.0 μM. We measured 22 parameters quantifying various aspects of the Ca2+ transients and shortening profiles (e.g. time to peak, amplitude, etc.) Although some statistical tests produced p values less than 0.05 for region, no systematic differences were observed between cells from the left and right ventricles. Our conservative interpretation is that single cardiac myocytes from the left and right ventricles have similar contractile properties. The different pressures generated by the two ventricles probably reflect differences in chamber structure and wall thickness as opposed to differences in the contractile properties of the myocytes themselves.Support or Funding InformationAHA GRNT2546003, NSF 1538754, NIH TR000117, APS STRIDE, APS UGSRF, HL115473.