摘要
目的观察盐酸关附甲素(AHH)对豚鼠离体心房肌动作电位及有效不应期的影响,探讨其抗心律失常作用的机制。方法脱颈法处死豚鼠后,迅速开胸取出心脏,移至台氏液中。从左心耳剪取大约3mm×10mm大小的肌条,固定于浴槽中,用持续通以混合气体(95%O2+5%CO2)的台式液灌流,流速为10ml/min,以频率为1Hz、脉宽2ms的阈上刺激平衡至少45min。利用玻璃微电极技术测定基础动作电位和有效不应期后,以25、75、250、500μmol/L的AHH灌流液灌流5min后,以同样条件测定药后动作电位和有效不应期。结果 500μmol/LAHH使零相最大除极速度(Vmax)下降12.4%,平均复极化斜率(ASRP)下降19.2%(p<0.01),对动作电位时程(APD)有延长趋势但未达到统计学差异;250μmol/L和500μmol/L两个浓度延长心房有效不应期的作用达到统计学差异,其作用呈频率依赖性。结论 1、高浓度盐酸关附甲素降低心房肌Vmax,有降低动作电位幅度(APA)趋势,具有延缓心房内传导的作用;2、盐酸关附甲素对心房动作电位时程无明显影响,但降低动作电位复极2相斜率,相对延缓心房复极;3、高浓度盐酸关附甲素频率依赖性延长心房有效不应期,可能是其抗心律失常的主要作用机制。
Objective To observe the effect of Acehytisine Hydrochloride（AHH） on action potential（AP） and effective refractory period（ERP） in isolated atrium of guinea pig, and explore the antiarrhythmic mechanism of AHH. Methods Adult guinea pigs weighing 350-500 gram were killed by cervical dislocation and the heart were immediately excised and bathed in Tyrode’s solution. The solution was continuously gassed with 95% O2 and 5% CO2 to give a pH of 7.4 and was maintained at 36.5±0.5°C. The obtained left atrial appendage preparations were perfused with Tyrode’s solution at a rate of 10ml/min, simultaneously driven by external electrical stimulation with rectangular current pulses （2ms duration,1.5×threshold strength） at a constant frequency （1Hz） for at least 45 minutes. Glass microelectrodes were used for measuring baseline AP and ERP. After 5 min of AHH perfusion（25,75,250,500μmol/L, respectively）, AP and ERP were measured again. All experimental data were expressed as the mean±S.E.M, SPSS13.0 statistic software package was used for data analysis. Results 1.AHH decreased Vmax by 12.4% at 500μmol/L（p0.05）; reduced ASRP by 19.2%（p0.01）. 2. AHH also prolonged AERP at different concentration respectively, but only 250, 500μmol/L reached statistical significance and this action was rate-dependent. Conclusions 1.Acehytisine Hydrochloride at higher concentrations reduced Vmax and tended to decrease APA, possibly slowing intra-atrial conduction; 2.Acehytisine Hydrochloride had no signif icant effect on atrial action potential duration, but slightly reduced Slope of phase 2 repolarization so as to slow atrial repolarization relatively. 3.Acehytisine Hydrochloride at higher concentrations prolonged atrial effective refractory period in a rate-dependent manner, possibly being its main antiarrhythmic mechanism.
出处
《中国分子心脏病学杂志》
CAS
2012年第3期182-185,共4页
Molecular Cardiology of China
关键词
盐酸关附甲素
台式液
豚鼠心房肌
动作电位
有效不应期
Acehytisine Hydrochloride
Tyrode’s Solution
Isolated Atrium
Effective Refractory Period
Action Potential Duration
