title: Radiofrequency catheter ablation of pulmonary vein roots results in axonal degeneration of distal epicardial nerves.
abstract: BACKGROUND
  In treatment of atrial fibrillations (AF), radiofrequency ablation (RFA) at the pulmonary vein (PV) roots isolates AF triggers in the myocardial sleeves, but also can destroy PV ganglia and branches of the intrinsic cardiac nerve plexus.
  
  
  OBJECTIVE
  To determine the long-term impact of RFA at the PV roots on the structure of epicardial nerves located distally from the RFA site.
  
  
  METHODS
  Five black-faced sheep underwent epicardial RFA of the left and middle PV roots. Two to 3 months after RFA, we obtained samples of epicardial nerves from remote locations of the left dorsal (LD) neural subplexus that extends along the roots of the superior PVs toward the coronary sinus (CS) and dorsal left ventricle (LV). Right atrial epicardial nerves from the right ventral (RV) neural subplexus of the ablated animals and epicardial nerves from LD neural subplexus of five additional intact sheep were used as control. Nerve morphology was examined using histochemical, immunohistochemical and transmission electron microscopy.
  
  
  RESULTS
  Histochemical acetylcholinesterase staining did not reveal any epicardial nerve alterations. However, tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) staining showed clearly the reduced numbers of TH and ChAT immunoreactive (IR) nerve fibers within epicardial nerves derived from the remote LD subplexus; control samples from all examined animals were full of evenly distributed TH-IR and ChAT-IR nerve fibers. In sharp contrast to control nerves, numerous swollen or disintegrated axons and Schwann cells with pyknotic nuclei inside unmyelinated and myelinated nerve fibers were identified by electron microscopy of ultrathin sections of epicardial nerves from the CS and LV regions in all ablated animals.
  
  
  CONCLUSIONS
  Degeneration of remote atrial and ventricular epicardial nerves is evident 2-3 months after epicardial RFA at the PV roots. Such nerves are likely to be non-functional. Therefore, long-term autonomic dysfunction is a potential risk of PV isolation by RFA.
authors.affiliation: Department of Cardiology, Faculty of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Aras
authors.initials: A
authors.lastname: Puodziukynas
authors.forename: Tomas
authors.initials: T
authors.lastname: Kazakevicius
authors.forename: Raimundas
authors.initials: R
authors.lastname: Vaitkevicius
authors.forename: Kristina
authors.initials: K
authors.lastname: Rysevaite
authors.forename: Marius
authors.initials: M
authors.lastname: Jokubauskas
authors.forename: Inga
authors.initials: I
authors.lastname: Saburkina
authors.forename: Vaiva
authors.initials: V
authors.lastname: Sladkeviciute-Dirzinauskiene
authors.forename: Evaldas
authors.initials: E
authors.lastname: Dirzinauskas
authors.forename: Vytautas
authors.initials: V
authors.lastname: Zabiela
authors.forename: Vytautas
authors.initials: V
authors.lastname: Sileikis
authors.forename: Jurgita
authors.initials: J
authors.lastname: Plisiene
authors.forename: Neringa
authors.initials: N
authors.lastname: Pauziene
authors.forename: Remigijus
authors.initials: R
authors.lastname: Zaliunas
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.forename: Dainius H
authors.initials: DH
authors.lastname: Pauza
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D017115:Catheter Ablation / Q000009:adverse effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010496:Pericardium / Q000294:innervation*; D011667:Pulmonary Veins / Q000294:innervation / Q000473:pathology* / Q000601:surgery*; D012583:Schwann Cells / Q000473:pathology / Q000648:ultrastructure; D012756:Sheep; D013908:Thoracotomy; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase