左氧氟沙星对糖尿病兔的致心律失常作用

Arrhythmogenic effect of levofloxacin in diabetic rabbits

目的 糖尿病患者QT间期延长反映了心脏的电不稳定性,这与心律失常的发生有关.作为临床常用的抗生素之一,左氧氟沙星可引起QT间期延长,甚至引起致命性尖端扭转性室性心动过速（Tdp）.本研究旨在评估左氧氟沙星对糖尿病兔的致心律失常作用.方法 健康新西兰大白兔30只,体重2.0～2.5 kg,雌雄各半,应用随机数字法分为对照组（n=10）和实验组（n=20）.实验组经耳缘静脉注射5％四氧嘧啶160 mg/kg建立糖尿病兔模型,对照组兔注射相同剂量的生理盐水.72 h后监测兔空腹血糖,若空腹血糖值大于基础血糖值的3倍,视为建模成功.饲养4周后制作冠状动脉灌流的左心室楔形心肌模型,分别灌注左氧氟沙星（1.14 mg/ml）,比较灌注左氧氟沙星前后对照组兔和糖尿病兔跨壁心电图QT间期、左心室心肌内膜、外膜细胞的动作电位时限（APD）、跨壁复极离散度（TDR）及室性心律失常的发生率.结果 与对照组相比,糖尿病兔心肌QT间期延长19％,糖尿病内膜、外膜APD明显延长,跨壁复极离散度增大,早后除极发生率为36％,心室颤动（室颤）发生率18％.灌注左氧氟沙星后,对照组心肌QT间期、内膜、外膜APD均延长,跨壁复极离散度增大,早后除极发生率60％,所有心肌均未发生室颤;糖尿病组心肌QT间期、内膜、外膜APD、跨壁复极离散度均显著增大,早后除极的发生率为63％,心室颤动发生率为45％,室性心律失常发生率显著增加（P＜0.05）.结论 左氧氟沙星引起糖尿病兔QT间期延长,跨壁复极离散度异常增大.与对照组相比,糖尿病组灌注左氧氟沙星后更易发生心律失常.

Objective The abnormal prolongation in QT interval in diabetics reflects the electric instability of heart,which is related to the incidence of cardiac arrhythmia.As one of the frequently used antibiotics in clinical practice,levofloxacin may prolong QT interval,or even lead to lethal ventricular arrhythmia-torsade de pointes（Tdp）.The present study was to assess the arrhythmogenic effect of levofloxacinin on diabetic rabbits.Methods Thirty healthy New Zealand rabbits weighing 2.0-2.5 kg were randomized into the control group （n=10）and the test group（n =20）.The rabbits in test group were injected with 5% tetraoxypyrimidine in a dosage of 160 mg/kg via the marginal vein to establish the diabetic rabbits model,while the control group was injected with the same volume of saline.The arterially perfused rabbit ventricular wedge preparations were produced four weeks later,which were infused with levofloxacin（1.14 mg/ml）,and transmural ECG and action potential period from both endocardium（APDEndo）and epicardium（APDEpi）were simultaneously recorded and compared.Results The QT interval,APDEndo,APDEpi,,and transmural dispersion of repolarization（TDR） of diabetic rabbits were prolonged,the incidence rate of early after-depolarization（EAD） and ventricular fibrillation（VF） increased （P〈0.05）.After perfusion with levofloxacin,the QT interval,APDEndo and APDEpi,TDR were longer,the incidence rate of EAD and VF were increased in test group（P〈0.05）.Conclusion In comparison to the control group,ventricular arrhythmia is liable to be induced after levofloxacin perfusion in the diabetic group.