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In patients with heart failure, digoxin and the other glycosides exert their positive inotropic effect by inhibiting Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2010ATPase, thereby increasing intracellular sodium, which, in turn, inhibits the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger and increases intracellular calcium levels. As the therapeutic index of digitalis is narrow, arrhythmias are common problems in clinical practice. The mechanisms and mediators of these arrhythmias, however, are not completely understood.<\/jats:p><jats:p> <jats:bold>2<\/jats:bold>\u2003The involvement of the sympathetic and parasympathetic nervous system in digitalis cardiac toxicity is reviewed.<\/jats:p><jats:p> <jats:bold>3<\/jats:bold>\u2003Receptors, channels, exchange systems or other cellular components involved in digitalis\u2010induced cardiotoxicity are also reviewed.<\/jats:p><jats:p> <jats:bold>4<\/jats:bold>\u2003Possible mediators of digitalis\u2010induced cardiac toxicity are discussed.<\/jats:p><jats:p> <jats:bold>5<\/jats:bold>\u2003Management of digitalis toxicity in patients is summarized.<\/jats:p><jats:p> <jats:bold>6<\/jats:bold>\u2003The determination of the possible mediators of digitalis\u2010induced cardiac toxicity will enhance our knowledge and lead to the development of new therapeutic strategies to treat these lethal arrhythmias.<\/jats:p>","DOI":"10.1111\/j.1474-8673.2004.00334.x","type":"journal-article","created":{"date-parts":[[2005,3,9]],"date-time":"2005-03-09T23:53:25Z","timestamp":1110412405000},"page":"35-52","source":"Crossref","is-referenced-by-count":41,"title":["Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels"],"prefix":"10.1111","volume":"25","author":[{"given":"A. 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