Objective To evaluate the effects of 24 h and 48 h atrial fibrillation(AF) on L-type calcium current (ICa-L)in atrial myocytes,and to investigate its possible mechanism and concordance.Methods Eighteen healthy adult mongrel canines were randomly divided into three groups:control group,24 h AF group and 48 h AF group,6 in each group.AF model was established by right atrial pacing with 600 bpm.The effective refractory period(ERP) of right atrial was measured by program stimulation.The atrial myocytes isolated from 24 h and 48 h AF canine,L-type calcium channel currents in atrial myocytes were recorded by patch clamp technique in the whole cell mode.The expressions of L-type voltage-dependent Ca2+ channel(LVDCC) α1c protein in atrium were measured by immunohistochemistry in three groups,semi-quantitative analysis of α1c protein expression was performed with pathological image analytic system.Results In 24 h AF group and 48 h AF group,AF can be induced in all the experiment animal.The pattern of ERP with an rapid drop in 6 h followed by a more gradual decline during hours 6 through 48 as the result of rapid pacing.The mean ERP was decreased by (12.13 ± 2.24) ms after 6 hours of pacing (from 141.00 ± 15.23 to 129.50 ± 8.64) ms (P ＜ 0.01).Similarly,after 24 h pacing the mean ERP was decreased by (19.23 ± 2.14) ms (P＜ 0.01),and by (28.15 ±4.26) ms after 48 h pacing(P＜0.01).Compared with control group(-6.69±0.08)pA/pF,the peak density of ICa-L was significantly reduced in 24 h AF group(-4.83±0.30)pA/pF,and it was reduced more in 48 h AF group(-3.70±0.50)pA/pF.Compared with control group,the protein expression of LVDCC α1c decreased significantly in group of 48 h and 24 h AF(P＜0.05),but in the group of 48 h AF it decreased more (P＜0.01).Conclusion The decrease of ICa-L may contribute to ionic basis of acute electrical remodeling of atrial cardiomyocytes caused by 24 h and 48 h AF in canine,which suggested that calcium channels blocker might prevent AF recurrence.%目的 研究犬心房颤动(房颤)持续24h和48 h,心房肌有效不应期和L型钙电流变化的一致性及其机制.方法 健康成年杂种犬18只,分为对照组、24 h房颤组、48 h房颤组,每组6只.600次/min起搏高右心房建立犬房颤模型,应用程序刺激的方法测定右心房有效不应期(ERP),通过Langendorff左回旋支灌流分离心房肌细胞,并通过全细胞膜片钳技术记录L型钙电流(ICa-L)变化.应用免疫组织化学方法检测各组心房组织L型电压依赖性钙通道(LVDCC)α1c蛋白表达.用图像分析系统对组织化学抗原表达进行半定量分析.结果 所有实验动物均可诱发出房颤.心房ERP的变化在最初6h较对照组明显缩短,后直至48 h呈进行性缩短.快速起搏6h后ERP(129.50±8.64)ms较对照组(141.00±15.23)ms缩短(12.13±2.24)ms(P＜0.01),24 h后心房ERP(123.00± 13.37) ms缩短(19.23±2.14)ms(P＜0.01),48 h缩短(28.15±4.26)ms(P＜0.01).同时在房颤持续过程中24h房颤可引起ICa-L电流密度(-4.83±0.30)pA/pF较对照组(-6.69±0.08)pA/pF减小,48 h(-3.70±0.50)pA/pF减少的程度更重.24 h房颤及48 h房颤犬的左、右心房组织LVDCC α1c蛋白表达均较对照组明显减少(P＜0.05),48 h房颤组减少程度更重(P＜0.01).结论 房颤持续24 h,心房肌ERP显著缩短、ICa-L密度降低.房颤持续48 h仍然维持L型钙通道改变特征.提示:钙通道阻断剂可用于持续24 h房颤,预防房颤复发.
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