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Characterization of atrial histopathological and electrophysiological changes in a mouse model of aging

作者:Tao Luo, Chang Cui-xian, Xin Zhou, Gu ShiKui, Tieming Jiang, Yuming Li · 发表于:International Journal of Molecular Medicine · 年份:2012 · DOI:10.3892/ijmm.2012.1174 · 被引用次数:33 · 研究领域:Atrial Fibrillation Management and Outcomes、Cardiac electrophysiology and arrhythmias、Cardiac Arrhythmias and Treatments

The detailed mechanisms of age-related atrial structural and electrophysiological changes remain elusive. Small animal models have recently been used for the investigation of atrial tachyarrhythmia. In this study, we investigated the hypothesis that atrial structural and electrical characterization with aging provides a substrate for atrial fibrillation using a mouse model of aging. Male Kunming mice aged 2 (young), 12 (middle-aged) and 24 months (aged) were used in this study. A surface electrocardiogram and sinus node recovery time (SNRT) were recorded at baseline. Atrial fibrillation (AF) inducibility and duration were measured by a transesophageal electrode catheter. Collagen content was assessed by the collagen volume fraction. Whole cell configuration using the patch clamp technique was performed for the transient outward potassium (Ito) and ultra-rapid delayed rectifier potassium (Ikur) currents. P-wave duration, SNRT and rate-corrected SNRT were longer in the aged group than in the remaining 2 groups, paralleled by inducibility significantly being increased in the aged group. The right atrium had significantly higher levels of fibrosis than the left atrium in all the groups (P<0.05), whereas the extent of fibrosis in the left atrium had a higher positive correlation with age relative to the right atrium (P<0.05). Moreover, in old age, the dispersion of left relative to right atrium repolarization and augmented Ito currents contributed to vulnerability to AF. Neverthel...