title: Importance of atrial surface area and refractory period in sustaining atrial fibrillation: testing the critical mass hypothesis.
abstract: OBJECTIVE
  The critical mass hypothesis for atrial fibrillation (AF) was proposed in 1914; however, there have been few studies defining the relationship between atrial surface area and AF. This study evaluated the effect of tissue area and effective refractory period (ERP) on the probability of sustaining AF in an in vivo model.
  
  
  METHODS
  Domestic pigs (n = 9) underwent median sternotomy. Epicardial activation maps were constructed from bipolar electrograms recorded from form-fitting electrode templates placed on the atria. Baseline ERPs were determined. ERP was lowered with a continuous infusion of acetylcholine (0.005-0.04 mg/Kg/min) until AF could be sustained after burst pacing. The atria were sequentially partitioned using bipolar radiofrequency ablation. ERPs were lowered using acetylcholine until AF could be sustained in each subdivision of atrial tissue. Each subdivision was further divided until AF was no longer inducible. At study completion, the heart was excised and the surface area of each section was measured.
  
  
  RESULTS
  Over a range of ERPs from 75 to 250 ms, the probability of AF was correlated with increasing tissue area (range, 19.5-105 cm(2)) and decreasing ERP. Logistic regression analysis identified shorter ERP (P < .001) and larger area (P = .006) as factors predictive of an increased probability of sustained AF (area under the curve of the receiver-operator characteristic = 0.878).
  
  
  CONCLUSIONS
  The probability of sustained AF was significantly associated with increasing tissue area and decreasing ERP. These data may lead to a greater understanding of the mechanism of AF and help to design better interventional procedures.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Barnes-Jewish Hospital, St Louis, MO 63110, USA.
authors.forename: Anson M
authors.initials: AM
authors.lastname: Lee
authors.forename: Abdulhameed
authors.initials: A
authors.lastname: Aziz
authors.forename: Jacob
authors.initials: J
authors.lastname: Didesch
authors.forename: Kal L
authors.initials: KL
authors.lastname: Clark
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Damiano
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000200:Action Potentials; D000818:Animals; D019540:Area Under Curve; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology* / Q000601:surgery; D002304:Cardiac Pacing, Artificial; D017115:Catheter Ablation; D018679:Cholinergic Agonists / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D016015:Logistic Models; D012372:ROC Curve; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D034421:Sus scrofa; D013997:Time Factors
chemical_list: D018679:Cholinergic Agonists; D000109:Acetylcholine