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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 guanidine hydrochloride (AHH) on the action potentials and effective refractory period of isolated atrial myocardium in guinea pigs and to explore its anti-arrhythmic mechanism. Methods After the guinea pigs were sacrificed, the heart was removed rapidly and then transferred to Tyrode’s solution. The muscle strips of about 3 mm × 10 mm in size were excised from the left atrial appendage and fixed in a bath. The perfusate was perfused with a continuous flow of a mixed gas (95% O2 + 5% CO2) at a flow rate of 10 ml / min at a frequency of 1 Hz, Pulse 2ms threshold supratentorial balance of at least 45min. After determining the basal action potentials and the effective refractory period by using the glass microelectrode technique, the action potential and the effective refractory period of the drug were determined under the same conditions after perfusion with 25, 75, 250 and 500 μmol / L AHH perfusate for 5 min. Results 500μmol / LAHH decreased the maximal depolarization speed (Vmax) of the zero phase by 12.4% and the average repolarization slope (ASRP) decreased by 19.2% (p <0.01), but prolonged the action potential duration (APD) There was statistical difference between the two concentrations of 250μmol / L and 500μmol / L for prolonging the atrial effective refractory period. The effect was frequency-dependent. High concentrations of hydrochloric acid Guanfupai reduce atrial Vmax, there is a tendency to reduce the action potential amplitude (APA), with the delay in the role of atrial conduction; 2, Guan A, hydrochloride on atrial action potential duration had no significant effect, But decreased the bipolar slope of bipolar action potential and retarded atrial repolarization. (3) High concentration of guanosine hydrochloride prolonged the effective refractory period of atrial in a frequency-dependent manner, which may be the main mechanism of anti-arrhythmia.