Hemodynamic Effects of Calcium-Sensitizing Agents

Pharmacology of Levosimendan: A New Myofilament Calcium Sensitizer

“…The actions of levosimendan on left ventricular diastolic function were, however, partially mediated through an intact autonomic nervous system. These findings are supported by other investigations conducted in conscious dogs with normal left ventricular function (60,64). The hemodynamic and left ventricular functional actions ( Fig.…”

Calcium‐Sensitizing Drugs: Positive Inotropy by Enhanced Sensitivity of the Contractile Apparatus to Calcium

“…Both in whole hearts and in vivo, levosimendan caused direct positive inotropic effects and improved ventricular filling (43,83,120). The most important characteristic of levosimendan is that it, unlike EMD57033, did not impair relaxation kinetics in vitro (44) or in vivo (43,83,120). These studies may indicate that levosimendan selectively enhances systolic function and diastolic filling without affecting ventricular relaxation indices.…”

“…Like EMD57033, levosimendan increased developed tension in papillary muscles without a change in the calcium transient, confirming calcium sensitization as a major mechanism of positive inotropy (44). Both in whole hearts and in vivo, levosimendan caused direct positive inotropic effects and improved ventricular filling (43,83,120). The most important characteristic of levosimendan is that it, unlike EMD57033, did not impair relaxation kinetics in vitro (44) or in vivo (43,83,120).…”

“…An interesting observation in this study was that levosimendan was three times more potent in failing hearts than in healthy control hearts. Total peripheral resistance, which was elevated following coronary artery occlusion, was significantly reduced after levosimendan ad-ministration ( 120). Levosimendan also protected isolated rabbit hearts from ischemia (89).…”

“…Also, the currently known calcium sensitizers are not pure or highly selective compounds, as phosphodiesterase-I11 inhibitory activity still resides to a various extent in all of them. This may represent a double-edged sword: it may counterbalance the negative lusitropic effects of calcium sensitization and may have advantageous hernodynamic effects via vasodilatation, but may also contribute to unwanted effects such as proarrhythmogenicity (120).…”