title: Endocardial stimulation of efferent parasympathetic nerves to the atrioventricular node in humans: optimal stimulation sites and the effects of digoxin.
abstract: The purposes of this study were to identify optimal sites of stimulation of efferent parasympathetic nerve fibers to the human atrioventricular node via an endocardial catheter and to investigate the interaction between digoxin and vagal activation at the end organ.
  
  
  METHODS
  The ventricular rate was measured during atrial fibrillation, prior to and during parasympathetic nerve stimulation, in 8 patients taking digoxin and in 10 controls. High frequency electrical stimuli were delivered via an hexapolar or quadripolar electrode catheter, placed at the posteroseptal right atrium near the atrioventricular node (n=18 patients) or in the coronary sinus (n=12 of 18 patients). In 4 patients, stimulation was repeated after intravenous administration of 1 to 2 mg of atropine.
  
  
  RESULTS
  Nerve stimulation prolonged the R-R interval in all patients. Stimulation close to the posteroseptal right atrium led to maximal atrioventricular nodal slowing. The mean R-R intervals at baseline and during parasympathetic nerve stimulation (60 mA) from the posteroseptal right atrium and the proximal coronary sinus were 581+/-79 ms, 2440+/-466, and 900+/-228 ms respectively (p=0.0001). The response to nerve stimulation was greater in patients taking digoxin than in patients not taking the drug (p=0.02). Junctional rhythm occurred during nerve stimulation in 8/8 patients taking digoxin and 0/10 not taking the drug (p=0.0001). The response to stimulation was eliminated after atropine (p=0.01).
  
  
  CONCLUSIONS
  Parasympathetic nerves to the atrioventricular node were stimulated from the proximal coronary sinus as well as the posteroseptal right atrium. Stimulation at the posteroseptal right atrium resulted in the greatest response, and digoxin enhanced this response. The augmented response suggests that an interaction may exist between parasympathetic stimulation and digoxin at the end organ.
authors.affiliation: Division of Cardiology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, USA. kquan@metrohealth.org
authors.forename: K J
authors.initials: KJ
authors.lastname: Quan
authors.forename: G F
authors.initials: GF
authors.lastname: Van Hare
authors.forename: L A
authors.initials: LA
authors.lastname: Biblo
authors.forename: J A
authors.initials: JA
authors.lastname: Mackall
authors.forename: M D
authors.initials: MD
authors.lastname: Carlson
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001283:Atrioventricular Node / Q000187:drug effects*; D001285:Atropine / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004361:Drug Tolerance; D004562:Electrocardiography; D004699:Endocardium / Q000187:drug effects*; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009476:Neurons, Efferent / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D001285:Atropine