Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat.
BACKGROUND
Prolonged atrial fibrillation (AF) results in electrical, structural, and gap-junctional remodeling. We examined the reversibility of the changes in (ultra)structure and gap junctions.


RESULTS
Four groups of goats were used: (1) sinus rhythm (SR), (2) 4 months' AF (4 mo AF), (3) 2 months' SR after 4 mo AF (2 mo post-AF), and (4) 4 months' SR after 4 mo AF (4 mo post-AF). Atria were characterized electrophysiologically, (ultra)structure was studied by light and electron microscopy, and structural and gap-junctional protein expression was studied by immunohistochemistry or Western blotting. The atrial effective refractory period had completely returned to normal values 2 mo post-AF. Induced AF episodes still lasted for minutes at 2 and 4 mo post-AF, compared with seconds in the SR group. Structural abnormalities were still present at 2 and 4 mo post-AF, although to a lesser extent. The increased atrial myocyte diameter was back to normal at 4 mo post-AF. The number of myocytes with severe myolysis had almost normalized 4 mo post-AF, whereas myocytes with mild myolysis remained significantly increased. Extracellular matrix area fraction after 4 mo AF was similar to SR. However, the extracellular matrix fraction per myocyte had increased after 4 mo AF and remained higher post-AF. Changes in expression of structural proteins were partially restored post-AF. The reduction of connexin 40 that was observed during AF was completely reversed at 4 mo post-AF.


CONCLUSIONS
Recovery from structural remodeling after 4 mo AF is a slow process and is still incomplete 4 mo post-AF. Several months post-AF, the duration of AF episodes is still prolonged (minutes).
Ausma
Jannie
J
Cardiovascular Research Institute Maastricht, The Netherlands. jannie.ausma@fys.unimaas.nl
van der Velden
Huub M W
HM
Lenders
Marie-Hélène
MH
van Ankeren
Erwin P
EP
Jongsma
Habo J
HJ
Ramaekers
Frans C S
FC
Borgers
Marcel
M
Allessie
Maurits A
MA
D000818:Animals; D001281:Atrial Fibrillation / Q000473:pathology* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D048429:Cell Size; D017630:Connexins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D022062:Electrophysiologic Techniques, Cardiac; D017629:Gap Junctions / Q000648:ultrastructure*; D006003:Glycogen / Q000378:metabolism; D006041:Goats; D006325:Heart Atria / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D009206:Myocardium / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020127:Recovery of Function; D012016:Reference Values; D012074:Remission Induction
D017630:Connexins; D006003:Glycogen