Atrial Remodeling and the Substrate for Atrial Fibrillation in Rat Hearts with Elevated Afterload

Background Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We have investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats. Methods and Results Male Wistar rats (3 - 4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham-operation (Sham). Experiments were performed on excised hearts 8, 14 and 20 weeks following surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5x5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks post-surgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks post surgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin-43, was markedly reduced in AoB compared with Sham hearts. Conclusions Using a small animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin-43 expression and marked conduction abnormalities.