Abstract 1258: Changes in Atrial Connexin40 and 43 are Apparent after 2 Months of Atrial Fibrillation in a Goat Model
Introduction: Atrial fibrillation (AF) has a tendency to persist. The predisposition for persistent AF occurs over a longer timescale than electrical remodelling. A “second factor” may influence the persistency of AF and it has been suggested that gap junction remodelling via altered connexin (Cx) expression may be involved in this process. We have previously shown that the relative ratio of connexins, expressed as Cx40/(Cx40+Cx43), in the human right atrial free wall correlates with atrial conduction velocity. We used a goat model of AF to investigate the time course of these changes in Cxs.
Methods and Results: Control goats in sinus rhythm (SR) were compared to goats maintained in AF for periods of 1 month by programmed right atrial burst pacing. Between periods of AF goats were DC cardioverted to SR and their atrial effective refractory period was allowed to return to baseline before induction of a further month of AF. Tissue was taken from the right and left atria and snap frozen in liquid nitrogen. Western blotting analysis was carried out for Cx40 and Cx43 and a relative ratio of Cx40/(Cx40+Cx43) was calculated. In the right atrium there was no significant difference between control (0.69±0.08, n=4) and goats with 1 month AF (0.72±0.09, n=4). However, in the right atrium there was a significant decrease in the relative ratio for goats with 2 months AF (0.42±0.09, p=0.016, n=3) and with 3 months AF (0.54±0.065, p=0.023, n=4) compared to control. Differences in the left atrium did not achieve significance between control and any time point of AF.
Conclusion: AF is associated with changes in the relative ratio of connexins in the right atrium in a goat model. The timescale of these changes suggest that gap junction remodelling remains a candidate for the “second factor”.