双黄连粉针剂对豚鼠心肌电生理的影响

目的探讨双黄连粉针剂对豚鼠心脏电生理的影响,以及其心脏安全性及作用机制。方法①在体实验:双黄连粉针剂325.5,1627.5和3255.0mg·kg-1分别在两组动物进行,每组15只。一组动物按照生理盐水→双黄连粉针剂325.5→1627.5mg·kg-1,另一组按照生理盐水→双黄连粉针剂3255.0mg·kg-1的顺序经颈外静脉缓慢推注,持续5min。于给生理盐水及静脉推注各剂量药物后5min记录心电图,分析P-R间期和校正QT间期(QTc)。②离体实验:按照灌流液(空白对照)→双黄连粉针剂0.3→1.5→3→9g·L-1→洗脱的顺序灌流,持续5min。于灌流5min末记录豚鼠离体心脏心电图,分析7只豚鼠的P-R间期和QTc间期;记录左心室乳头肌动作电位,分析5只豚鼠的动作电位复极50%水平时程(APD50)和90%水平时程(APD90)。结果①在体豚鼠心电图表明,双黄连粉针剂325.5和1627.5mg·kg-1显著延长P-R间期,从生理盐水处理时的(59±5)ms分别延长到(74±10)ms和(88±20)ms(P<0.05),各浓度组的QTc间期无明显变化;双黄连粉针剂3255.0mg·kg-1处理P-R间期则从生理盐水处理时的(58±5)ms延长到(133±29)ms(P<0.05),QTc从(247±16)ms延长到(301±65)ms(P<0.05),并显示明显的室内传导阻滞。②离体豚鼠心电图表明,双黄连粉针剂3和9g·L-1使空白对照组P-R间期从(84±17)ms延长到(113±39)ms和(130±23)ms(P<0.05),伴有明显的室内传导阻滞,而各浓度组的QTc间期无明显变化。双黄连粉针剂各浓度组对正常豚鼠左心室乳头肌动作电位APD50与APD90无明显作用。结论注射用双黄连粉针剂能引起豚鼠房室和室内传导阻滞,其作用机制可能是抑制心肌细胞钠通道。

Electrophysiological effects of Shuang-huang-lian intravenous injection on guinea pig hearts

OBJECTIVE To explore cardiac safety and its underlying mechanisms of Shuang-huang-lian (SHL) intravenous injection by recording cardiac electrophysiological parameters. METHODS ① In vivo ECG recordings were made in guinea pigs to analyze effects of jugular intravenous (iv) injection of SHL 325.5, 1627.5 and 3255.0 mg·kg^-1 on P-R and corrected QT (QTc) interval prolongation. Animals in 2 groups were treated as the following processes: normal saline→SHL 325.5→1627.5 mg·L^-1, or normal saline→SHL 3225.0 mg·L^-1 for 5 min, respectively. ② In vitro studies were also conducted on isolated guinea pig hearts. ECG and papillary muscle action potential recordings were made to analyze the effects of SHL on P-R and QTc interval prolongation and action potential duration at 50% (APD₅₀) and 90% (APD₉₀) repolarization levels. The isolated guinea pig hearts were exposed to blank control→SHL 0.3→1.5→3→9 g·L^-1 by Langendorff perfusion. RESULTS (1) In vivo ECG of guinea pigs showed that SHL 325.5 and 1627.5 mg·kg^-1 significantly prolonged the P-R interval from (59±5)ms to (74±10)ms and (88±20)ms, respectively (P<0.05). SHL 3255.0 mg·kg^-1 prolonged not only the P-R interval from (58±5)ms to (133±29)ms (P<0.05), but the QTc from (247±16)ms to (301±65)ms (P<0.05), and showed intraventricular conduction block. (2) In vitro experiments showed that SHL did not change the QTc, APD₅₀ and APD₉₀. However, SHL 3 and 9 g·L^-1 remarkably prolonged the P-R interval from (84±17)ms to (113±39)ms and (130±23)ms, respectively (P<0.05). Also, intraventricular conduction block was observed in SHL 3 and 9 g·L^-1 groups, respectively. CONCLUSION Intravenous administration of SHL showed intraventricular conduction block in guinea pig hearts, suggesting that sodium channel blockade underlie its effects.