IL-6加重蟾酥注射液潜在性心律失常作用

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection

目的研究蟾酥注射液以及合用IL-6条件下,其潜在心律失常风险及其机理。方法采用豚鼠在体心电图以及左心室肌细胞动作电位、钙电流和钠电流实验,分析心电图心率、P-R、QRS以及QTc间期,及其变化基于的机理。结果①在体心电图表明1倍临床剂量蟾酥注射液未能引起心电图明显改变;而单独IL-6(18.4μg·kg^(-1))及合用1倍临床剂量蟾酥注射液明显引起P-R及QTc间期延长。②蟾酥注射液1倍临床浓度对动作电位复极90%水平时程(APD 90)无明显作用;而单独IL-6(20μg·L^(-1))以及合用1倍临床浓度蟾酥注射液明显延长动作电位APD 90。③蟾酥注射液1倍临床浓度对Ca^(2+)电流无明显抑制作用,而IL-6(20μg·L^(-1))合用1倍临床浓度蟾酥注射明显抑制Ca^(2+)电流。④蟾酥注射液1、5、10倍临床浓度未能明显抑制Na^(+)电流;IL-6(20μg·L^(-1))及合用蟾酥注射液对Na+电流无明显作用。结论蟾酥注射液临床上使用存在低心律失常风险,但患者存在以IL-6增加为特征的炎症条件下,IL-6加重蟾酥注射液对Ca^(2+)电流的抑制作用,导致房室传导阻滞的风险明显增加。

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG,the action potential,L-type Ca^(2+) and Na^(+) currents from left ventricular myocytes were used to analyze heart rate(HR),P-R,QRS and QTc intervals and the underlying mechanism.Results①CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However,the IL-6(18.4μg·kg^(-1))only and the combinational use of IL-6(18.4μg·kg^(-1))plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.②The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90%repolarization level(APD_(90)).The IL-6(20μg·L^(-1))only and the combination of CS at one time CRC plus IL-6(20μg·L^(-1))significantly prolonged APD_(90).③Moreover,the IL-6(20μg·L^(-1))combined with CS at one time CRC significantly inhibited the L-type Ca^(2+)current.④CS at one,five,ten time CRC,IL-6(20μg·L^(-1))alone and IL-6(20μg·L^(-1))combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However,in presence of high titer of IL-6 characterized by inflammation,CS may induce the atrioventricular conduction block due to the blockade effect on Ca^(2+)current by both of CS and IL-6.