首页> 中文期刊> 《山东医药》 >环丙沙星对豚鼠心电图和乳头肌动作电位的影响

环丙沙星对豚鼠心电图和乳头肌动作电位的影响

         

摘要

Objective To observe the effects of ciprofloxacin on electrocardiogram ( ECG) and action potential in papil-lary muscles of guinea pigs, and to investigate the cardio toxicity of ciprofloxacin in order to provide a reference for the safety of clinical application.Methods A total of 42 guinea pigs were randomly divided into 7 groups, with 6 guinea pigs in each group.50, 100, and 200 mg/kg sparfloxacin were injected intraperitoneally into guinea pigs with the low, medium and high dose groups of sparfloxacin, while the low, middle and high dose ciprofloxacin groups were intraperitoneally injected with 50, 100, and 200 mg/kg ciprofloxacin.The control group was injected intraperitoneally with equal doses of NS.Ⅱlead ECG were recorded before and after 5, 10, and 30 minutes of intraperitoneal injection by RM-6240 software.The parameters of ECG were measured, including heart rate, P wave height, PR interval, R wave height, QRS wave width, QT interval and T wave height.A total of 18 guinea pigs were cut off the right ventricular papillary muscle and randomly divided into 3 groups, with 6 guinea pigs in each group.The control group was treated with Tyrode′s solution at constant temperature and constant speed. Sparfloxacin was added to the Tyrode′s solution in the sparfloxacin group, and the concentration of sparfloxacin was increased to 1, 10 and 100μmol/L, respectively.Ciprofloxacin was added to the Tyrode′s solution in ciprofloxacin group, and the final concentration of drug was 1, 10 and 100μmol/L respectively.The time of resting potential (RP), amplitude of action poten-tial ( APA) , action potential duration of 50%repolarization ( APD50 ) , and action potential duration of 90% repolarization (APD90) of guinea pigs′papillary muscles were recorded by RM-6240 software after adding drugs in 15 min.Results At 10 and 30 min after injecting 100 mg/kg sparfloxacin, the QT interval of ECG were prolonged significantly, as compared with the data before injection and that of the control group (all P<0.01).After injecting 200 mg/kg sparfloxacin 5, 10, and 30 min, the QT interval of ECG were prolonged significantly, as compared with the data before injection and the control group (all P<0.01).After injecting 200 mg/kg ciprofloxacin 10, and 30 min, the QT interval of ECG were prolonged significantly as compared with the data before injection and that of the control group (all P<0.05).Ciprofloxacin of medium and high dose groups had a lighter prolonged effect on QT interval than sparfloxacin of medium and high dose groups ( P<0.05 or P<0.01).When the concentration of sparfloxacin in perfusate were 1, 10, and 100 μmol/L, the APD50 and APD90 were pro-longed significantly as compared with that of the control group (all P<0.01).When the concentration of ciprofloxacin in per-fusate was 100μmol/L, the APD90 was prolonged as compared with that of the control group (P<0.01).The effect of 100μmol/L ciprofloxacin in prolonging APD50 as well as APD90 was less than that of 100 μmol/L sparfloxacin (all P<0.01). Conclusions When ciprofloxacin is in high dose, it can cause action potential duration prolong in papillary muscles of guinea pigs, as well as elongate QT interval of ECG in guinea pigs, with potential cardiac toxicity.%目的:观察环丙沙星对豚鼠心电图和乳头肌动作电位的影响。方法选择豚鼠42只,随机分为司帕沙星低、中、高剂量组,环丙沙星低、中、高剂量组及对照组,每组6只。司帕沙星低、中、高剂量组分别腹腔注射50、100、200 mg/kg的司帕沙星,环丙沙星低、中、高剂量组分别腹腔注射50、100、200 mg/kg的环丙沙星,对照组腹腔注射等量生理盐水。采用RM-6240软件记录各组给药前及给药5、10、30 min时Ⅱ导联心电图,收集心电图各参数,包括HR、P波高度、PR间期、R波高度、QRS波宽度、QT间期和T波高度。另取豚鼠18只,随机分为司帕沙星组、环丙沙星组、对照组,每组6只,分别剪下右心室乳头肌后灌流。对照组采用台氏液恒温、恒速灌流;司帕沙星组台式液+司帕沙星灌流,采用累积浓度给药法依次使药物终浓度为1、10、100μmol/L;环丙沙星组台式液+环丙沙星灌流,采用累积浓度给药法依次使药物终浓度为1、10、100μmol/L。采用RM-6240软件记录各组灌流15 min时的静息电位( RP)、动作电位幅值( APA)、动作电位复极至50%的时程( APD50)及动作电位复极至90%的时程( APD90)。结果腹腔注射100 mg/kg司帕沙星10、30 min时,QT间期均较给药前及对照组延长(P均<0.01);腹腔注射200 mg/kg司帕沙星5、10、30 min时,QT间期均较给药前及对照组延长(P均<0.01)。腹腔注射200 mg/kg环丙沙星10、30 min时,QT间期均较给药前及对照组延长(P均<0.05)。环丙沙星中、高剂量组延长QT间期的作用均小于司帕沙星中、高剂量组(P<0.05或<0.01)。灌流液中司帕沙星浓度为1、10、100μmol/L时,乳头肌APD50、APD90与对照组比较均明显延长(P均<0.01)。灌流液中环丙沙星浓度为100μmol/L时,其乳头肌APD90较对照组明显延长(P<0.01)。100μmol/L环丙沙星延长APD50、APD90的作用均小于100μmol/L司帕沙星(P均<0.01)。结论大剂量环丙沙星可引起豚鼠乳头肌动作电位时程延长,明显延长QT间期,具有潜在的心脏毒性。

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