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Subcellular mechanisms underlying digitalis-induced arrhythmias: role of calcium/calmodulin-dependent kinase II (CaMKII) in the transition from an inotropic to an arrhythmogenic effect.
Heart Lung Circ
December 2014
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata 1900, Argentina. Electronic address:
Cardiotonic glycosides or digitalis are positive inotropes used in clinical practice for the treatment of heart failure, which also exist as endogenous ligands of the Na(+)/K(+) ATPase. An increase in the intracellular Ca2+ content mediates their positive inotropic effect, but has also been proposed as a trigger of life-threatening arrhythmias. Although the mechanisms involved in the positive inotropic effect of these compounds have been extensively studied, those underlying their arrhythmogenic action remain ill defined.
View Article and Find Full Text PDFThe chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic agent, are reviewed. Bretylium tosylate is used to treat life-threatening ventricular arrhythmias, principally ventricular fibrillation and ventricular tachycardia, that have not responded to treatment with first-line antiarrhythmic agents. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission.
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