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Dynamic nature of atrial fibrillation substrate during development and reversal of heart failure in dogs.

AbstractBACKGROUND:
Clinical atrial fibrillation (AF) often results from pathologies that cause atrial structural remodeling. The reversibility of arrhythmogenic structural remodeling on removal of the underlying stimulus has not been studied systematically.
METHODS AND RESULTS:
Chronically instrumented dogs were subjected to 4 to 6 weeks of ventricular tachypacing (VTP; 220 to 240 bpm) to induce congestive heart failure (CHF), followed by a 5-week recovery period leading to hemodynamic normalization at 5-week recovery (Wk5(rec)). The duration of burst pacing-induced AF under ketamine/diazepam/isoflurane anesthesia increased progressively during VTP and recovered toward baseline during the recovery period, paralleling changes in atrial dimensions. However, even at full recovery, sustained AF could still be induced under relatively vagotonic morphine/chloralose anesthesia. Wk5(rec) dogs showed no recovery of CHF-induced atrial fibrosis (3.1+/-0.3% for controls versus 10.7+/-1.0% for CHF and 12.0+/-0.8% for Wk5(rec) dogs) or local conduction abnormalities (conduction heterogeneity index 1.8+/-0.1 in controls versus 2.3+/-0.1 in CHF and 2.2+/-0.2 in Wk5(rec) dogs). One week of atrial tachypacing failed to affect the right atrial effective refractory period significantly in CHF dogs but caused highly significant effective refractory period reductions and atrial vulnerability increases in Wk5(rec) dogs.
CONCLUSIONS:
Reversal of CHF is followed by normalized atrial function and decreased duration of AF; however, fibrosis and conduction abnormalities are not reversible, and a substrate that can support prolonged AF remains. Early intervention to prevent fixed structural abnormalities may be important in patients with conditions that predispose to the arrhythmia.
AuthorsKaori Shinagawa, Yan-Fen Shi, Jean-Claude Tardif, Tack-Ki Leung, Stanley Nattel
JournalCirculation (Circulation) Vol. 105 Issue 22 Pg. 2672-8 (Jun 04 2002) ISSN: 1524-4539 [Electronic] United States
PMID12045175 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Topics
  • Animals
  • Atrial Fibrillation (etiology, physiopathology)
  • Cardiac Pacing, Artificial
  • Disease Models, Animal
  • Disease Progression
  • Disease Susceptibility (physiopathology)
  • Dogs
  • Electrophysiologic Techniques, Cardiac
  • Fibrosis (complications, pathology)
  • Heart Conduction System (physiopathology)
  • Heart Failure (complications, pathology, physiopathology)
  • Hemodynamics
  • Recovery of Function
  • Time Factors

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