BACKGROUND: Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF). The autonomic nervous system is involved in the pathogenesis of both AF and CHF. We examined the role of autonomic remodeling in contributing to AF substrate in CHF. METHODS AND RESULTS: Electrophysiological mapping was performed in the pulmonary veins and left atrium in 38 rapid ventricular-paced dogs (CHF group) and 39 control dogs under the following conditions: vagal stimulation, isoproterenol infusion, β-adrenergic blockade, acetylcholinesterase (AChE) inhibition (physostigmine), parasympathetic blockade, and double autonomic blockade. Explanted atria were examined for nerve density/distribution, muscarinic receptor and β-adrenergic receptor densities, and AChE activity. In CHF dogs, there was an increase in nerve bundle size, parasympathetic fibers/bundle, and density of sympathetic fibrils and cardiac ganglia, all preferentially in the posterior left atrium/pulmonary veins. Sympathetic hyperinnervation was accompanied by increases in β(1)-adrenergic receptor R density and in sympathetic effect on effective refractory periods and activation direction. β-Adrenergic blockade slowed AF dominant frequency. Parasympathetic remodeling was more complex, resulting in increased AChE activity, unchanged muscarinic receptor density, unchanged parasympathetic effect on activation direction and decreased effect of vagal stimulation on effective refractory period (restored by AChE inhibition). Parasympathetic blockade markedly decreased AF duration. CONCLUSIONS: In this heart failure model, autonomic and electrophysiological remodeling occurs, involving the posterior left atrium and pulmonary veins. Despite synaptic compensation, parasympathetic hyperinnervation contributes significantly to AF maintenance. Parasympathetic and/or sympathetic signaling may be possible therapeutic targets for AF in CHF.
BACKGROUND:Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF). The autonomic nervous system is involved in the pathogenesis of both AF and CHF. We examined the role of autonomic remodeling in contributing to AF substrate in CHF. METHODS AND RESULTS: Electrophysiological mapping was performed in the pulmonary veins and left atrium in 38 rapid ventricular-paced dogs (CHF group) and 39 control dogs under the following conditions: vagal stimulation, isoproterenol infusion, β-adrenergic blockade, acetylcholinesterase (AChE) inhibition (physostigmine), parasympathetic blockade, and double autonomic blockade. Explanted atria were examined for nerve density/distribution, muscarinic receptor and β-adrenergic receptor densities, and AChE activity. In CHFdogs, there was an increase in nerve bundle size, parasympathetic fibers/bundle, and density of sympathetic fibrils and cardiac ganglia, all preferentially in the posterior left atrium/pulmonary veins. Sympathetic hyperinnervation was accompanied by increases in β(1)-adrenergic receptor R density and in sympathetic effect on effective refractory periods and activation direction. β-Adrenergic blockade slowed AF dominant frequency. Parasympathetic remodeling was more complex, resulting in increased AChE activity, unchanged muscarinic receptor density, unchanged parasympathetic effect on activation direction and decreased effect of vagal stimulation on effective refractory period (restored by AChE inhibition). Parasympathetic blockade markedly decreased AF duration. CONCLUSIONS: In this heart failure model, autonomic and electrophysiological remodeling occurs, involving the posterior left atrium and pulmonary veins. Despite synaptic compensation, parasympathetic hyperinnervation contributes significantly to AF maintenance. Parasympathetic and/or sympathetic signaling may be possible therapeutic targets for AF in CHF.
Authors: Paul A Gould; Michael Yii; Catriona McLean; Samara Finch; Tanneale Marshall; Gavin W Lambert; David M Kaye Journal: Pacing Clin Electrophysiol Date: 2006-08 Impact factor: 1.976
Authors: Rishi Arora; Joseph S Ulphani; Roger Villuendas; Jason Ng; Laura Harvey; Sarah Thordson; Firdous Inderyas; Yi Lu; David Gordon; Pablo Denes; Rodney Greene; Susan Crawford; Robert Decker; Alexander Morris; Jeffrey Goldberger; Alan H Kadish Journal: Am J Physiol Heart Circ Physiol Date: 2007-11-02 Impact factor: 4.733
Authors: Thomas J Wang; Martin G Larson; Daniel Levy; Ramachandran S Vasan; Eric P Leip; Philip A Wolf; Ralph B D'Agostino; Joanne M Murabito; William B Kannel; Emelia J Benjamin Journal: Circulation Date: 2003-05-27 Impact factor: 29.690
Authors: Rishi Arora; Jason Ng; Joseph Ulphani; Ilias Mylonas; Haris Subacius; Greg Shade; David Gordon; Alexander Morris; Xiang He; Yi Lu; Rashad Belin; Jeffrey J Goldberger; Alan H Kadish Journal: J Am Coll Cardiol Date: 2007-03-12 Impact factor: 24.094
Authors: Hemantha Koduri; Jason Ng; Ivan Cokic; Gary L Aistrup; David Gordon; J Andrew Wasserstrom; Alan H Kadish; Richard Lee; Rod Passman; Bradley P Knight; Jeffrey J Goldberger; Rishi Arora Journal: Circ Arrhythm Electrophysiol Date: 2012-06-21
Authors: Hyung-Wook Park; Mark J Shen; Shien-Fong Lin; Michael C Fishbein; Lan S Chen; Peng-Sheng Chen Journal: Curr Opin Cardiol Date: 2012-01 Impact factor: 2.161
Authors: Jean C Hardwick; E Marie Southerland; Allison E Girasole; Shannon E Ryan; Sara Negrotto; Jeffrey L Ardell Journal: Am J Physiol Regul Integr Comp Physiol Date: 2012-08-29 Impact factor: 3.619
Authors: Gary L Aistrup; Ivan Cokic; Jason Ng; David Gordon; Hemanth Koduri; Suzanne Browne; Dorina Arapi; Yogita Segon; Jacob Goldstein; Abigail Angulo; J Andrew Wasserstrom; Jeffrey J Goldberger; Alan H Kadish; Rishi Arora Journal: Heart Rhythm Date: 2011-08-25 Impact factor: 6.343