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Circulation. 2003;107:2051-2058
Published online before print April 7, 2003, doi: 10.1161/01.CIR.0000062689.04037.3F
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(Circulation. 2003;107:2051.)
© 2003 American Heart Association, Inc.


Basic Science Reports

Reverse Structural and Gap-Junctional Remodeling After Prolonged Atrial Fibrillation in the Goat

Jannie Ausma, PhD; Huub M.W. van der Velden, PhD; Marie-Hélène Lenders, BSc; Erwin P. van Ankeren, BSc; Habo J. Jongsma, PhD; Frans C.S. Ramaekers, PhD; Marcel Borgers, PhD; Maurits A. Allessie, MD, PhD

From the Cardiovascular Research Institute Maastricht (J.A., M.-H.L., F.C.S.R., M.B., M.A.A.) and University Medical Center Utrecht (H.M.W.v.d.V., E.P.v.A., H.J.J.), the Netherlands.

Correspondence to J. Ausma, CARIM, PO Box 616, 6200 MD Maastricht, The Netherlands. E-mail jannie.ausma{at}fys.unimaas.nl

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.

Methods and 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).


Key Words: atrium • fibrillation • structure • gap junctions • remodeling




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