| Objective:Atrial fibrillation(AF) is the most common cardiac arrhythmia in clinical practice. It is an independent risk factor for thromboembolic disease and has higher mortality. AF is often accompanied by hypertension, heart failure, myocardial infarction. The electrophysiological and histological mechanism of AF has been researched in those abnormal states. Age is independently associated with the prevalence of AF and the morbidity of AF in people older than 65 increases significantly. But the mechanism of AF is different from that in heart failure, myocardial infarction and so on. Now, there is few report about age-related animal models of AF, electrophysiologic properties and the extracellular matrix in atrium and there relationship are not very clear. So the present study was to investigate the age-related electrophysiological changes of atrium and induction of AF and atrial tachycardia by burst pacing in mice. Dynamic changes of interstitial fibrosis in atrium and the relationship between interstitial fibrosis and age were analyzed.Methods:Forty male Kun-ming mice were bred. The mice that growed to 1 month, 8-9 months,20 months were included in the experiment. Excluding 10 mice died in experiment and normal life, thirty mice (weight from 28.9g to 67.8g) were divided into three groups according age. The surface ECG was monitored by polygraph. Sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT) and induction of atrial arrhythmia were determined by transesophageal atrial rapid stimulation. Dynamic change of atrial fibrosis was analyzed by picrosirius-red stained section.Results:The duration of P duration in elderly mice was significantly longer than in young and adult mice [elderly mice (24.3±1.3s) vs young mice (18.3±1.6s), adult mice (19.3±1.5s), P<0.05]. The SNRT 100ms and CSNRT 100ms in elderly mice were significantly longer than in the others (P<0.05). The induction of atrial arrhythmia was 27.3% in young mice,72.7% in adult mice,87.5% in elderly mice. It showed the induction of atrial arrhythmia increased with age and it was significantly more in the adult group and elderly group than in the young group. But the induction of AF and the mean duration of AF were no difference among groups. The atrial fibrosis increased with age in the right and left atria. The atrial fibrosis in right atria was more than that in left atria among the three groups (P<0.05). The content of collagen in left atrium has significant difference between groups[aged group:0.67% (0.26%-1.52%); young group 1.19%(0.83%-2.09%); mid-aged group 2.1% (1.60%-2.90%), P<0.05] and presented positive correlation with aging.(P<0.05, r=0.592). The deposition of collagen in elderly and adult mice was significantly more than in yong mice[young goup 2.02%(1.50%-3.20); mid-aged group 3.68% (2.40%-5.60%); aged group 2.9%(1.78%-8.14%), P<0.05]. Spearman rank order correlation presented content of collagen was positively correlated with aging (P<0.05, r=0.326).Conclusions:The study indicates that (1) The elderly group mice have longer P wave duration, SNRT100ms, CSNRT100ms and the more induction of atrial arrhythmia. Those suggest delaying of conduction velocity in atria, the higher atrial vulnerability and sinus node dysfunction in elderly mice. (2) The content of collagen in atrium has an age-related increase and positive correlation with aging. This indicates that atrial fibrosis is a mechanism of age-related AF. (3) The animal model by transesophageal atrial rapid stimulation is a feasible method to study electrophysiological property and the mechanisms of AF with small animal such as mouse. This is a easily, minimally invasive method that could further research age-related AF and genetic or molecular mechanisms of AF with mice or transgenic mice.
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