| Objective: Atrial fibrillation(AF) is a radid ardiac arrhythmia characterized by irregular atrial activation. Atrial fibrillation can lead to serious complications, such as atrial thrombosis, stroke, heart failure, so it increase morbidity and mortality of patients with atrial fibrillation. The pathophysiology of AF is complex, and the mechanisms of AF are not completely understood at present. Recent research has suggested atrail remodeling, including to atrial electrical remodeling and structural remodeling.,this idear had made significant progress in the field of AF pathophysiology. however, Accumulating evidence has highlighted a central role for abnormal Ca2+ overload in atrail remodeling. Recent evidence indicate that atrim of enrgy metabolism change is associated with intracellular Ca2+ overload. The purpose of this study was to simulate rabbit model of atrial fibrillation by rapid atrial pacing, additionally to investigate the effects of antiarrthythmic drug trimetazidine on intracellular free Ca2+ concentratio in the management area of AF and to propose a new way of prevention and treatment of AF.Methods:A total of 30 normal rabbits were used in this study. After measured rabbit weight and heart rate, rabbits were randomly divided into three groups. The saline group(Control group, n=10), saline pacing group(SN-P group, n=10), trimetazidine pacing group(TMZ-P group, 8mg/(kg.d), n=10). TMZ-P group were injected trimetazidine into stomach each day for three week and the other two group instead of saline as the same volume as the drugs. Then, rabbit was fixed on station, endotracheal intubation, cutted the right internal jugular vein, right atrium localized in the electrode catheter by right internal jugular vein, needle electrode was inserted limbs. Recorded surface ECG and right atrial electrogram, the electrode catheter was fixed. Then, each rabit of the saline pacing group and trimetazidine pacing group was paced with the rate of 600 per minute for 8 hours. Then killed the rabbits immediately and took out the heart, intracellular free Ca2+ concentration was measured in rabbit atrial muscle of three groups with flow cytomety and with Fluo-3/AM as calcium indicator.SPSS13.0 software packs were used for all the data to make statistical-analysis. All values are expressed asmean±standard deviation. Continuous values were compared with repeated measurement date MANOVA in same group. One-way ANOVA was used to evaluate differences between groups of discrete variables. We took α=0.05 as statistic significant level.Results:Fluorescence intensity of three geoup was measured by flow cytometry Intracellular free Ca2+ concentration is calculated by fluorescence intensity value(Fig.1, Fig.2, Fig.3). The fluorescence intensity of intracellular free Ca2+ was 128±43.45、232.04±29.45、122.32±36.85(Table 1)in rabbit atrial muscle cell of three groups. The fluorescence intensity of intracellular free Ca2+ in rabbit atrial muscle of NS-P group increased significantly as compared with the NS group(P < 0.01)(Table 1). The fluorescence intensity of intracellular free Ca2+ in rabbit atrial muscle had significant deviation between TMZ-P group and NS-P group(P<0.01)(Table 1). The fluorescence intensity of intracellular free Ca2+ in rabbit atrial muscle had no significant deviation between TMZ-P group and NS group(P>0.05)(Table 1). This indicated that trimetazidine could inhibit the decreasing of the calcium overload in rabbit atrial muscle cell resulted in rapid atrial pacing.Conclusion:Rapid atrial pacing can lead to increased intracellular free Ca2+ concentration in rabbit atrial muscle, but trimetazidine can effectively prevent the heightening of straggling tendency of intracellular free Ca2+ concentration in rabbit atrial muscle resulted in rapid atrial pacing. |
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