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• W2316502304 abstract "Abstract: We characterized the Ca 2+ -sensitizing and phosphodiesterase (PDE)-inhibitory potentials of levosimendan and enoximone to assess their contributions to the positive inotropic effects of these drugs. In guinea pig hearts perfused in the working-heart mode, the maximal increase in cardiac output (55%, P < 0.05) was attained at 50 nM levosimendan. The corresponding value for enoximone (36%) was significantly smaller ( P < 0.05) and was observed at a higher concentration (500 nM). In permeabilized myocyte-sized preparations levosimendan evoked a maximal increase of 55.8 ± 8% (mean ± SEM) in isometric force production via Ca 2+ sensitization (pCa 6.2, EC 50 8.4 nM). Enoximone up to a concentration of 10 μM failed to influence the isometric force. The PDE-inhibitory effects were probed on the PDE III and PDE IV isoforms. Levosimendan proved to be a 1300-fold more potent and a 90-fold more selective PDE III inhibitor (IC 50 for PDE III 1.4 nM, and IC 50 for PDE IV 11 μM, selectivity factor ∼8000) than enoximone (IC 50 for PDE III 1.8 μM, and IC 50 for PDE IV 160 μM, selectivity factor ∼90). Hence, our data support the hypothesis that levosimendan exerts positive inotropy via a Ca 2+ -sensitizing mechanism, whereas enoximone does so via PDE inhibition with a limited PDE III versus PDE IV selectivity." @default.
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• W2316502304 date "2005-09-01" @default.
• W2316502304 modified "2023-10-17" @default.
• W2316502304 title "Two Inotropes With Different Mechanisms of Action: Contractile, PDE-Inhibitory and Direct Myofibrillar Effects of Levosimendan and Enoximone" @default.
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• W2316502304 doi "https://doi.org/10.1097/01.fjc.0000175454.69116.9" @default.
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