阿奇霉素与生脉注射液合用致豚鼠心律失常作用及其机制

发布时间：2018-06-12 13:12

本文选题：生脉注射液 + 阿奇霉素　；参考：《中国药理学与毒理学杂志》2017年06期

【摘要】：目的研究阿奇霉素合用生脉注射液潜在的致心律失常风险及其机制。方法 (1)豚鼠在体实验:1倍临床剂量的阿奇霉素(38.2 mg·kg~(-1))或生脉注射液(4.6 m L·kg~(-1))颈外静脉缓慢推注;或1倍临床剂量阿奇霉素缓慢推注5 min后加生脉注射液缓慢推注。记录给药前后的心电图。(2)豚鼠离体实验:离体心脏按1,5和10倍临床浓度,即阿奇霉素41.5→207.5→415 mg·L~(-1)顺序灌流,或生脉注射液5→25→50 m L·L~(-1)顺序灌流;或阿奇霉素+生脉注射液(均1倍临床浓度)灌流。上一浓度组灌流结束后随后灌流下一浓度组,每组灌流持续5 min,分别记录各组给药5 min后的心电图。(3)细胞实验,酶解法分离制备豚鼠单个左心室肌细胞,按1倍临床浓度阿奇霉素(41.5 mg·L~(-1))→阿奇霉素+生脉注射液(均1倍临床浓度)顺序灌流,每组灌流持续5 min,分别记录各组给药5 min后的动作电位、L型Ca~(2+)及Na+电流。结果 (1)在体实验:心电图显示,1倍临床剂量阿奇霉素或生脉注射液均未能引起心电图明显改变,而阿奇霉素合用生脉注射液(均1倍临床剂量)显著降低心率(P0.05),延长P-R(P0.05)及QRS(P0.05)间期。(2)离体实验:心电图显示,1,5和10倍临床浓度阿奇霉素浓度依赖性降低心率(P0.05),延长P-R(P0.05)及QRS(P0.05)间期,5倍临床浓度还能显著延长QTc间期(P0.05),洗脱能部分逆转上述变化。1,5和10倍临床浓度生脉注射液浓度依赖性地降低心率(P0.05),延长P-R(P0.05)间期,对QRS及QTc间期无明显作用,洗脱能部分恢复上述变化。而阿奇霉素合用生脉注射液(均1倍临床浓度)显著降低心率(P0.05),延长P-R(P0.05)及QRS(P0.05)间期。(3)细胞实验:1倍临床浓度阿奇霉素对豚鼠单个左心室肌细胞动作电位幅值及复极50%(APD_(50))及90%(APD_(90))时程无明显作用。而阿奇霉素合用生脉注射液(均1倍临床浓度)显著降低动作电位幅值(P0.05),缩短APD_(50)(P0.05)及APD_(90)(P0.05)。同样,阿奇霉素1倍临床浓度对L型Ca~(2+)及Na~+电流无明显抑制作用,阿奇霉素合用生脉注射液(均1倍临床浓度)显著抑制L型Ca~(2+)(P0.05)及Na+(P0.05)电流。结论阿奇霉素或生脉注射液在临床上使用存在一定心律失常的风险,两者合用其风险进一步加大。抑制L型Ca~(2+)及Na+电流是两者合用导致心律失常的作用机制之一。
[Abstract]:Objective to study the potential arrhythmia risk and its mechanism of azithromycin combined with Shengmai injection. Methods 1) in vivo, 1) azithromycin (38.2 mg 路kg ~ (-1) or Shengmai injection (4.6 mL 路kg ~ (-1) was injected into external jugular vein of guinea pig (n = 1), or Azithromycin was injected slowly for 5 min and then added Shengmai injection (n = 5). Electrocardiogram (ECG) of guinea pig before and after administration: the isolated heart was perfused in the order of 1: 5 and 10 times clinical concentration, that is, azithromycin 41.5 ~ 207.5 ~ 415mg / L ~ (-1), or Shengmai injection (5 ~ 25 ~ 50ml / L ~ (-1). Or azithromycin Shengmai injection (1 times clinical concentration). After the last group was perfused, the next group was perfused for 5 minutes. The electrocardiogram (ECG) of each group was recorded for 5 min, and the isolated guinea pig left ventricular myocytes were prepared by enzymolysis. Azithromycin injection (Azithromycin 41.5 mg / L) and azithromycin Shengmai injection (both 1 times clinical concentration) were perfused for 5 mins in each group. The action potential of Azithromycin (Azithromycin) and Na current were recorded after 5 min administration of Azithromycin (Azithromycin) for 5 min. Results 1) in vivo experiment: electrocardiogram showed that azithromycin or Shengmai injection did not cause significant changes in electrocardiogram (ECG). In vitro, azithromycin combined with Shengmai injection (1 times clinical dose) significantly decreased the heart rate (P 0.05) and prolonged the interval of P 0 05 (P 0 05) and QRSN P 0 05) in vitro. The electrocardiogram showed that Azithromycin 1 and 10 times the clinical concentration of azithromycin in a concentration-dependent manner decreased the heart rate (P 0 05) and prolonged the heart rate (P 0 05). P-RN P0.05) and QRS- P0.05) could significantly prolong the QTc interval P0.05N, and the elution could partially reverse the above changes. The concentration of Shengmai injection decreased the heart rate of P0.05N in a concentration-dependent manner, and prolonged the P-RN P0.05) interval. There was no obvious effect on QRS and QTc interval, but the elution energy partially recovered the above changes. Azithromycin combined with Shengmai injection (1 times clinical concentration) significantly decreased the heart rate of P0.05N, prolonged the interval of P-RGN P0.05 and QRS7 P0.05).) Cell experiment: 1 times clinical concentration of azithromycin on action potential amplitude and repolarization of single left ventricular myocytes of guinea pig There was no obvious effect on the time course of 50 and 90 APD. Azithromycin combined with Shengmai injection (1 times clinical concentration) significantly decreased the amplitude of action potential (P0.05), shortened APD50 (P0.05) and reduced APDP0.05. Similarly, azithromycin 1 times of clinical concentration had no obvious inhibitory effect on L-type Cajian2) and Na ~ + current. Azithromycin combined with Shengmai injection (both 1 times clinical concentration) significantly inhibited L-type Cahuan2 (P0.05) and Na (P0.05) currents. Conclusion Azithromycin or Shengmai injection has a certain risk of arrhythmia in clinical use. Inhibition of L type Caan2) and Na current is one of the mechanisms of arrhythmia induced by both.
【作者单位】：南京中医药大学药学院国家科技部规范化中药药理实验室;南京军区总医院干部病房呼吸科;南京中医药大学第一附属医院(江苏省中医院)心脏内科;泰州中国医药城中医药研究院;
【基金】：江苏省高校自然科学研究重大项目(14KJA360002) 江苏省自然科学基金(BK20151355);江苏省自然科学基金(BK20131262) 泰州中国医药城第四批次高层次创新人才“113人才计划”(2016024)~~
【分类号】：R965

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