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Mechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium
Author(s) -
Lewinski Dirk,
Bisping Egbert,
Elgner Andreas,
Kockskämper Jens,
Pieske Burkert
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.08.004
Subject(s) - inotrope , medicine , heart failure , endocrinology , toxicity , intracellular , calcium , chemistry , biochemistry
Background Cardiac glycosides are characterized by a narrow therapeutic range with Ca 2+ ‐overload and arrhythmias occurring at higher concentrations. Data on cardiac glycosides in isolated failing human myocardium are scarce and the frequency‐dependent actions and toxicity of Strophanthidin have not yet been characterized. Aims To determine inotropic responses and toxicity of Strophanthidin in failing human myocardium. Methods and results Experiments were performed in trabeculae from 64 end‐stage failing hearts. Developed force, and intracellular [Ca 2+ ] i and [Na + ] i were recorded with Strophanthidin (0.01 to 1 μmol/L; 37°C, 1 Hz) and compared to interventions with distinct mechanisms of action (elevated [Ca 2+ ] o , Isoproterenol, and EMD57033). The effects of Strophanthidin on force–frequency behaviour were also assessed. Strophanthidin exerted concentration‐dependent positive inotropic effects. These were paralleled by increases in intracellular [Na + ] as well as increasing [Ca 2+ ] i ‐transients and SR‐Ca 2+ ‐load. At high concentrations (>0.5 μmol/L), Strophanthidin caused afterglimmers and aftercontractions, with declining developed force despite further increasing [Ca 2+ ] i ‐transients. The force–frequency‐relationship and diastolic function at higher pacing rates was worsened by Strophanthidin in a concentration‐dependent manner. Conclusions Strophanthidin toxicity was dependent on concentration, calcium load, beating rate and β‐adrenergic receptor activation. Our data support the view that low doses, heart rate control and additional β‐adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure.