肾上腺素对抗双黄连中药注射剂所致心律失常

Adrenaline antagonizes proarrhythmic effect induced by Shuanghuanglian Injection

目的研究肾上腺素对抗双黄连中药注射剂所致的豚鼠心律失常的作用。方法①在体实验:按双黄连276 mg·kg-1→2760 mg·kg-1的顺序累计静脉缓慢推注,注射后稳定5 min,出现缓慢性心律失常后,再给予溶于生理盐水的盐酸肾上腺素0.0078 mg·kg-1和0.039 mg·kg-1的顺序进行累加静脉缓慢推注,持续5 min后记录心电图,分析心率(HR)、P-R、QRS和心率校正QT间期(QTc)。②离体实验:按顺序灌流双黄连0.3 g·L-1→1.5 g·L-1,诱发豚鼠离体心脏心律失常后,再灌流双黄连1.5 g·L-1+肾上腺素0.42 mg·L-1,最后用双黄连1.5 g·L-1和正常灌流液依次洗脱。每一组灌流持续5 min,分别记录各浓度组给药5 min后的心电图。分析HR,P-R,QRS及QTc间期。③左心室单细胞动作电位实验:依次灌流双黄连0.3 g·L-1→1.5 g·L-1→3 g·L-1→双黄连3 g·L-1+肾上腺素0.83 mg·L-1。分析复极50%及90%水平的动作电位时程(APD50,APD90)。结果①双黄连2760 mg·kg-1能明显降低豚鼠HR,延长P-R,QRS间期(P<0.05)。肾上腺素(0.0078及0.039 mg·kg-1)显著增加双黄连所致的缓慢心率,同时,明显改善双黄连导致的P-R和QRS间期的延长(P<0.05)。②双黄连1.5 g·L-1明显减慢离体心脏HR,延长P-R间期(P<0.05)。肾上腺素0.42 mg·L-1能明显加快双黄连所致的缓慢心率(P<0.05),同时明显缩短QTc(P<0.05)。③双黄连3 g·L-1显著延长豚鼠左心室APD50及APD90,肾上腺素0.83 mg·L-1使其恢复正常值。结论肾上腺素可对抗双黄连所致的缓慢性心律失常,可用于临床抢救双黄连中药注射剂的严重不良反应。

OBJECTIVE To explore the antagonistic effect of adrenaline（ Adr） on proarrhythmia induced by Chinese herbal intravenous injection of Shuanghuanglian Injection（ SHL）. METHODS ① In vivo ECG recording was made to analyze effects of jugular intravenous（ iv） injection of SHL alone and SHL plus adrenaline on ECG in guinea pigs. SHL and /or adrenaline were injected accumulatively in this order： SHL 276 mg·kg-1→2760 mg·kg^-1→adrenaline 0. 0078 mg·kg^-1→adrenaline 0. 039 mg·kg^-1. ② In vitro ECG recording was made to analyze effects of SHL and SHL plus adrenaline on ECG in isolated hearts of guinea pigs. SHL and /or adrenaline were perfused in this order： SHL 0. 3 g·L^-1→SHL 1. 5 g·L^-1→SHL 1.5 g·L^-1＋ Adr 0. 42 mg·L^-1→SHL 1.5 g·L^-1→control perfusion solution. ③ Single ventricular myocyte action potential was recorded to analyze the effect of SHL alone and SHL plus adrenaline on the action potential durations at 50%（ APD50） and 90%（ APD90） repolarization levels. SHL alone was perfused in such order： SHL 0. 3 g·L^-1→SHL 1. 5 g·L^-1→SHL 3 g·L^-1＋ adrenaline 0. 83 mg·L^-1. RESULTS ① SHL（ 2760 mg·kg^-1） significantly reduced heart rate and prolonged QRS and QTc intervals in vivo ECG. Adrenaline（ 0. 0078 mg·kg^-1and 0. 039 mg·kg^-1） significantly ameliorated the proarrhythmia of SHL by shortening QTc,P-R intervals and increasing heart rate. ② SHL（ 1.5 g·L^-1） remarkably reduced heart rate and prolonged P-R interval in isolated guinea pig hearts in vitro. Adrenaline（ 0. 42 mg·L^-1） significantly increased heart rate and shortened the QTc interval. ③ SHL（ 3 g·L^-1） remarkably prolonged the APD50and APD90. Adrenaline abolished the prolonged effect of SHL on APD50APD90. CONCLUSION Adrenaline might be clinically used to treat severe adverse drug reactions induced by SHL based on its antagonistic effect on arrhythmia.