title: Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function.
abstract: OBJECTIVE
  Pulmonary vein ganglia (PVG) are targets for atrial fibrillation ablation. However, the functional relevance of PVG to the normal heart rhythm remains unclear. Our aim was to investigate whether PVG can modulate sinoatrial node (SAN) function.
  
  
  RESULTS
  Forty-nine C57BL and seven Connexin40+/EGFP mice were studied. We used tyrosine-hydroxylase (TH) and choline-acetyltransferase immunofluorescence labelling to characterize adrenergic and cholinergic neural elements. PVG projected postganglionic nerves to the SAN, which entered the SAN as an extensive, mesh-like neural network. PVG neurones were adrenergic, cholinergic, and biphenotypic. Histochemical characterization of two human embryonic hearts showed similarities between mouse and human neuroanatomy: direct neural communications between PVG and SAN. In Langendorff perfused mouse hearts, PVG were stimulated using 200-2000 ms trains of pulses (300 μs, 400 µA, 200 Hz). PVG stimulation caused an initial heart rate (HR) slowing (36 ± 9%) followed by acceleration. PVG stimulation in the presence of propranolol caused HR slowing (43 ± 13%) that was sustained over 20 beats. PVG stimulation with atropine progressively increased HR. Time-course effects were enhanced with 1000 and 2000 ms trains (P < 0.05 vs. 200 ms). In optical mapping, PVG stimulation shifted the origin of SAN discharges. In five paroxysmal AF patients undergoing pulmonary vein ablation, application of radiofrequency energy to the PVG area during sinus rhythm produced a decrease in HR similar to that observed in isolated mouse hearts.
  
  
  CONCLUSIONS
  PVG have functional and anatomical biphenotypic characteristics. They can have significant effects on the electrophysiological control of the SAN.
authors.affiliation: Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zarzoso
authors.forename: Kristina
authors.initials: K
authors.lastname: Rysevaite
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Milstein
authors.forename: Conrado J
authors.initials: CJ
authors.lastname: Calvo
authors.forename: Adam C
authors.initials: AC
authors.lastname: Kean
authors.forename: Felipe
authors.initials: F
authors.lastname: Atienza
authors.forename: Dainius H
authors.initials: DH
authors.lastname: Pauza
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.forename: Sami F
authors.initials: SF
authors.lastname: Noujaim
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D001683:Biological Clocks / Q000502:physiology; D017115:Catheter Ablation; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D005260:Female; D005318:Fetal Heart / Q000033:anatomy & histology / Q000294:innervation; D005724:Ganglia / Q000033:anatomy & histology / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D011667:Pulmonary Veins / Q000294:innervation*; D012849:Sinoatrial Node / Q000033:anatomy & histology / Q000294:innervation* / Q000502:physiology*
keywords: Intrinsic cardiac ganglia; Pulmonary veins; Sinoatrial node
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