title: Digitalis and neurohormonal abnormalities in heart failure and implications for therapy.
abstract: A pathophysiologic hallmark of heart failure is neurohormonal excitation, a prominent feature of which is activation of the sympathetic nervous system. Studies from our laboratories demonstrate that clinical heart failure is characterized by marked increases in efferent sympathetic neural outflow to muscle; the magnitude of this sympatho-excitation parallels the degree of cardiac dysfunction. Impairments of cardiopulmonary and arterial baroreflex sensory mechanisms appear to be responsible to a significant degree for this sympatho-excitation, consistent with findings in animal models of heart failure. Digitalis glycosides exert modest inotropic actions when administered to patients with heart failure. Digitalis also has potent autonomic effects that can potentiate impaired arterial and cardiopulmonary baroreflex mechanisms in experimental models of cardiac dysfunction. Acute digitalis administration to patients with moderate-to-severe heart failure produces profound and sustained sympatho-inhibition, which precedes any observed hemodynamic action of the agent. Further, acute digitalization of such patients rapidly normalizes impaired baroreflex-mediated mechanisms. Data now suggest that the mechanism of action of digitalis in humans is an acute potentiation of baroreceptor-mediated afferent regulation of sympathetic neural mechanisms. Prospective, randomized and controlled studies now are required to test the hypothesis that the acute effects of digitalis on autonomic mechanisms also are observed during chronic administration. In theory, the chronic sympatho-inhibitory action of digitalis, combined with its chronic potentiation of impaired baroreflex mechanisms, may offer beneficial effects independent of its inotropic actions in patients with heart failure.
authors.affiliation: Department of Internal Medicine, University of Iowa Hospitals, Iowa City 52242.
authors.forename: D W
authors.initials: DW
authors.lastname: Ferguson
mesh_terms: D004071:Digitalis Glycosides / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D011311:Pressoreceptors / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D004071:Digitalis Glycosides; D006728:Hormones