title: Chronic electrical neuronal stimulation increases cardiac parasympathetic tone by eliciting neurotrophic effects.
abstract: BACKGROUND
  Recently, we provided a technique of chronic high-frequency electric stimulation (HFES) of the right inferior ganglionated plexus for ventricular rate control during atrial fibrillation in dogs and humans. In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off.
  
  
  OBJECTIVE
  We thus hypothesized that HFES might elicit trophic effects on cardiac neurons, which in turn increase baseline parasympathetic tone of the atrioventricular node.
  
  
  RESULTS
  In mongrel dogs atrial fibrillation was induced by rapid atrial pacing. Endocardial HFES of the right inferior ganglionated plexus, which contains abundant fibers to the atrioventricular node, was performed for 2 years. Sham-operated nonstimulated dogs served as control. In chronic neurostimulated dogs, we found an increased neuronal cell size accompanied by an increase of choline acetyltransferase and unchanged tyrosine hydroxylase protein expression as compared with unstimulated dogs. Moreover, β-nerve growth factor (NGF) and neurotrophin (NT)-3 were upregulated in chronically neurostimulated dogs. In vitro, HFES of cultured neurons of interatrial ganglionated plexus from adult rats increased neuronal growth accompanied by upregulation of NGF, NT-3, glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) expression. NGF was identified as the main growth-inducing factor, whereas NT-3 did not affect HFES-induced growth. However, NT-3 could be identified as an important acetylcholine-upregulating factor.
  
  
  CONCLUSIONS
  HFES of cardiac neurons in vivo and in vitro causes neuronal cellular hypertrophy, which is mediated by NGF and boosters cellular function by NT-3-mediated acetylcholine upregulation. This knowledge may contribute to develop HFES techniques to augment cardiac parasympathetic tone.
authors: Department of Cardiology, RWTH Aachen University, Pauwelsstr 30, D-52074 Aachen, Germany. orana@ukaachen.de
authors: Obaida R
authors: OR
authors: Rana
authors: Erol
authors: E
authors: Saygili
authors: Christopher
authors: C
authors: Gemein
authors: Matthias D H
authors: MD
authors: Zink
authors: Alexandra
authors: A
authors: Buhr
authors: Esra
authors: E
authors: Saygili
authors: Karl
authors: K
authors: Mischke
authors: Kay W
authors: KW
authors: Nolte
authors: Joachim
authors: J
authors: Weis
authors: Christian
authors: C
authors: Weber
authors: Nikolaus
authors: N
authors: Marx
authors: Patrick
authors: P
authors: Schauerte
mesh_terms: D000818:Animals; D016280:Atrial Function, Right / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3 / Q000502:physiology*; D017777:Parasympathetic Fibers, Postganglionic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors; D020933:Neurotrophin 3