Elevated afterload via aortic stenosis in rats increased pacing-induced AF at 20 weeks, causing left atrial remodeling, fibrosis, reduced connexin43 expression, and conduction abnormalities.
Does elevated afterload induced by partial aortic stenosis increase the inducibility of atrial fibrillation and cause atrial remodeling in rats?
Elevated afterload directly induces left atrial remodeling, fibrosis, and conduction abnormalities, increasing the vulnerability to atrial fibrillation even in the absence of systemic hypertension.
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 investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats. METHODS AND RESULTS: Male Wistar rats (aged 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 after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 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 postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. 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, connexin43, 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 connexin43 expression, and marked conduction abnormalities.
Kim et al. (2011) studied Atrial fibrillation. Partial stenosis of the ascending aorta (AoB) vs. Sham operation was evaluated on Incidence and duration of pacing-induced AF, atrial remodeling, and conduction abnormalities. Elevated afterload via aortic stenosis in rats increased pacing-induced AF at 20 weeks, causing left atrial remodeling, fibrosis, reduced connexin43 expression, and conduction abnormalities.