title: Complex interactions between the sinoatrial node and atrium during reentrant arrhythmias in the canine heart.
abstract: BACKGROUND
  Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation (AF). However, the direct role of the SAN has never been described.
  
  
  RESULTS
  The SAN was optically mapped in coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine (ACh; 0.3 to 3 micromol/L) and/or isoproterenol (Iso; 0.2 to 1 micromol/L). An optical action potential multiple component algorithm and dominant frequency analysis were used to reconstruct SAN activation and to identify specialized sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced AF/AFL by shortening atrial repolarization. The entire SAN structure created a substrate for macroreentry with 9.6+/-1.7 Hz (69 episodes in all preparations). Atrial excitation waves could enter the SAN through the sinoatrial conduction pathways and overdrive suppress the node. The sinoatrial conduction pathways acted as a filter for atrial waves by slowing conduction and creating entrance block. ACh/Iso modulated filtering properties of the sinoatrial conduction pathways by increasing/decreasing the degree of the entrance block, respectively. Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh (49+/-39%) and ACh/Iso (62+/-25%) (P=0.38). Without ACh, the AF/AFL waves captured the SAN and overdrive suppressed it. Spontaneous SAN activity could terminate or convert AFL to AF during cholinergic withdrawal.
  
  
  CONCLUSIONS
  The specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic stimulation not only can slow sinus rhythm and facilitate AF/AFL but also protects the intrinsic SAN function from the fast AF/AFL rhythm.
authors.affiliation: Department of Biomedical Engineering, Washington University, Campus Box 1097, 1 Brookings Dr, St Louis, MO 63130-4899, USA. vadimfed@gmail.com
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
authors.forename: Roger
authors.initials: R
authors.lastname: Chang
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Glukhov
authors.forename: Geran
authors.initials: G
authors.lastname: Kostecki
authors.forename: Deborah
authors.initials: D
authors.lastname: Janks
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology; D001282:Atrial Flutter / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D006325:Heart Atria / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D023421:Models, Animal; D012849:Sinoatrial Node / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*
chemical_list: D007545:Isoproterenol; D000109:Acetylcholine