Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von Lewinski, D; Bisping, E; Elgner, A; Kockskämper, J; Pieske, B.
Mechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium.
Eur J Heart Fail. 2007; 9(11):1086-1094
Doi: 10.1016/j.ejheart.2007.08.004
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- Führende Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
- von Lewinski Dirk
- Co-Autor*innen der Med Uni Graz
- Bisping Egbert Hubertus
- Kockskämper Jens
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- Abstract:
- Background: Cardiac glycosides are characterized by a narrow therapeutic range with Ca2+ -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 [Ca2+] and [Na+](i) were recorded with Strophanthidin (0.01 to 1 mu mol/L; 37 degrees C, 1 Hz) and compared to interventions with distinct mechanisms of action (elevated [Ca2+](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 [Ca2+](i)-transients and SR-Ca2+-load. At high concentrations (>0.5 mu mol/L), Strophanthidin caused afterglimmers and aftercontractions, with declining developed force despite further increasing [Ca2+](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 beta-adrenergic receptor activation. Our data support the view that low doses, heart rate control and additional P-adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Cardiotonic Agents - pharmacology Cardiotonic Agents - toxicity
- Diastole - drug effects
- Female -
- Heart Failure - metabolism Heart Failure - physiopathology
- Humans -
- Isoproterenol - pharmacology Isoproterenol - toxicity
- Male -
- Middle Aged -
- Myocardial Contraction - drug effects
- Sodium-Calcium Exchanger - drug effects
- Strophanthidin - pharmacology Strophanthidin - toxicity
- Systole - drug effects
- Find related publications in this database (Keywords)
- cardiac glycosides
- human myocardium
- calcium
- contractile function
- arrhythmias