title: Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness.
abstract: BACKGROUND
  Reentrant arrhythmias involving the sinoatrial node (SAN), namely SAN reentry, remain one of the most intriguing enigmas of cardiac electrophysiology. The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post-myocardial infarction (MI) structural remodeling.
  
  
  RESULTS
  In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post-left ventricular MI (6-15 weeks) dogs (n=5) compared with control dogs (n=4). In vitro, high-resolution near-infrared optical mapping of intramural SAN activation was performed in coronary perfused atrial preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16-28 mm) and micro-reentry (1-3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine [0.1 µmol/L] or isoproterenol [0.01-0.1 µmol/L]) after termination of atrial tachypacing (5-8 Hz), a finding not seen in controls. The autonomic stimulation induced heterogeneous changes in the SAN refractoriness; thus, competing atrial or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentry. The micro-reentry pivot waves were anchored to the longitudinal block region and produced both tachycardia and paradoxical bradycardia (due to exit block), despite an atrial ECG morphology identical to regular sinus rhythm. Intranodal longitudinal conduction blocks coincided with interstitial fibrosis strands that were exaggerated in the MI SAN pacemaker complex (fibrosis density: 37±7% MI versus 23±6% control; P<0.001).
  
  
  CONCLUSIONS
  Both tachy- and brady-arrhythmias can result from SAN micro-reentry. Postinfarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry.
authors: Department of Physiology and Cell Biology, College of Veterinary Medicine, Division of Cardiovascular Medicine, and College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH.
authors: Alexey V
authors: AV
authors: Glukhov
authors: Lori T
authors: LT
authors: Hage
authors: Brian J
authors: BJ
authors: Hansen
authors: Adriana
authors: A
authors: Pedraza-Toscano
authors: Pedro
authors: P
authors: Vargas-Pinto
authors: Robert L
authors: RL
authors: Hamlin
authors: Raul
authors: R
authors: Weiss
authors: Cynthia A
authors: CA
authors: Carnes
authors: George E
authors: GE
authors: Billman
authors: Vadim V
authors: VV
authors: Fedorov
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D015716:Electrocardiography, Ambulatory; D005355:Fibrosis; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000503:physiopathology; D012849:Sinoatrial Node / Q000503:physiopathology*; D020257:Ventricular Remodeling
keywords: autonomic effects; myocardial infarction; optical action potential mapping; sinoatrial nodal reentry tachycardia; sinoatrial node
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