Mechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium.
Eur J Heart Fail
; 9(11): 1086-94, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17956764
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 ANDRESULTS:
Experiments were performed in trabeculae from 64 end-stage failing hearts. Developed force, and intracellular [Ca2+]i and [Na+]i were recorded with Strophanthidin (0.01 to 1 micromol/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 micromol/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 beta-adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure.
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Banco de datos:
MEDLINE
Asunto principal:
Estrofantidina
/
Insuficiencia Cardíaca
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur J Heart Fail
Asunto de la revista:
CARDIOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania