title: Anatomic localization and autonomic modulation of atrioventricular junctional rhythm in failing human hearts.
abstract: BACKGROUND
  The structure-function relationship in the atrioventricular junction (AVJ) of various animal species has been investigated in detail; however, less is known about the human AVJ. In this study, we performed high-resolution optical mapping of the human AVJ (n = 6) to define its pacemaker properties and response to autonomic stimulation.
  
  
  RESULTS
  Isolated, coronary-perfused AVJ preparations from failing human hearts (n = 6, 53 ± 6 years) were optically mapped using the near-infrared, voltage-sensitive dye, di-4-ANBDQBS, with isoproterenol (1 μmol/L) and acetylcholine (1 μmol/L). An algorithm detecting multiple components of optical action potentials was used to reconstruct multilayered intramural AVJ activation and to identify specialized slow and fast conduction pathways (SP and FP). The anatomic origin and propagation of pacemaker activity was verified by histology. Spontaneous AVJ rhythms of 29 ± 11 bpm (n = 6) originated in the nodal-His region (n = 3) and/or the proximal His bundle (n = 4). Isoproterenol accelerated the AVJ rhythm to 69 ± 12 bpm (n = 5); shifted the leading pacemaker to the transitional cell regions near the FP and SP (n = 4) and/or coronary sinus (n = 2); and triggered reentrant arrhythmias (n = 2). Acetylcholine (n = 4) decreased the AVJ rhythm to 18 ± 4 bpm; slowed FP/SP conduction leading to block between the AVJ and atrium; and shifted the pacemaker to either the transitional cell region or the nodal-His region (bifocal activation).
  
  
  CONCLUSIONS
  We have demonstrated that the AVJ pacemaker in failing human hearts is located in the nodal-His region or His bundle regions and can be modified with autonomic stimulation. Moreover, we found that both the FP and SP are involved in anterograde and retrograde conduction.
authors.affiliation: Department of Biomedical Engineering, Washington University in St Louis, MO, USA.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ambrosi
authors.forename: Geran
authors.initials: G
authors.lastname: Kostecki
authors.forename: William J
authors.initials: WJ
authors.lastname: Hucker
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Glukhov
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Wuskell
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
authors.forename: Nader
authors.initials: N
authors.lastname: Moazami
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001283:Atrioventricular Node / Q000473:pathology* / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000502:physiology; D002036:Bundle of His / Q000473:pathology* / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial / Q000379:methods; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods
chemical_list: D007545:Isoproterenol; D000109:Acetylcholine