Diltiazem hydrochloride

The cardiac contractile performance was evaluated by studying isolated papillary muscles from the LV as previously described [27 (link),64 (link)]. The following mechanical parameters were measured during isometric contraction: maximum developed tension (DT; g/mm²), maximum rate of tension development (+dT/dt; g/mm²/s), and decline (−dT/dt; g/mm²/s). Regulator mechanisms of Ca²⁺ influx and L-type calcium channel activity were analyzed by Ca²⁺ concentration extracellular elevation maneuver (response percentage) and elevation of extracellular Ca²⁺ concentrations (0.5, 1.5, 2.5, and 3.5 mM) in the presence and absence of diltiazem (10⁻⁵ M; Diltiazem Hydrochloride, Sigma^® Aldrich, St Louis, MO, USA), a specific blocker of L-type calcium channels. A post-rest contraction maneuver (response percentage) and elevation of extracellular Ca²⁺ concentrations (0.5, 1.5, 2.5, and 3.5 mM) in the presence and absence of cyclopiazonic acid (CPA, 30 mM; Penicillium cyclopium, Sigma^® Aldrich, St Louis, MO, USA), a highly specific blocker of SERCA2a, were performed to assess the potential of SERCA2a function. All variables were normalized per cross-sectional area of the papillary muscle (CSA). Seven papillary muscles with CSA >1.5 mm² were excluded from analysis as they can present central core hypoxia and impaired functional performance [64 (link),65 (link)].