A real-time cell analysis system for evaluating anti-arrhythmic drugs by monitoring the growth and beating of primary neonatal rat cardiomyocytes
10.3867/j.issn.1000-3002.2014.06.004
- VernacularTitle:运用实时细胞分析系统监测原代乳鼠心肌细胞的生长及搏动评价抗心律失常药物
- Author:
Shuyan WANG
;
Xijie WANG
;
Kang JLN
;
Taotao HUL
;
Jing MA
- Publication Type:Journal Article
- Keywords:
drug evaluation,preclinical;
real-time systems;
lidocaine;
quinidine;
cardiotoxicity
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(6):837-843
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTlVE To establish a real-time cell analysis system ( RTCA) for early drug car-diotoxicity evaluation. METHODS An in vitro drug cardiotoxicity evaluation method was established using RTCA Cardio system and primary cultured cardiomyocytes of neonatal rats. The beating rate, am-plitude and beating rhythm irregularity ( BRl ) of cardiomyocytes were observered after antiarrhythmic drugs, such as quinidine and lidocaine were added, to assess the effect of the above method on cardio-toxicity evaluation. RESULTS RTCA Cardo E-Plate 96 was inoculated with primary cultured cardiomyo-cytes that began to beat after 24 h and beat regularly after 48 h. The stable beating was maintained for a minimum of three days. The beating of cardiomyocytes decreased rapidly from 155±5 to 0 after incuba-tion with quinidine. The beating recovered gradually after 6 h. Quinidine at 3.1μmol·L-1 caused the beat-ing rate to return to 124±16. Quinidine allowed the beating rate to return to normal when the concentra-tion was less than 100.0μmol·L-1 . The beating rate, amplitude and BRl of cardiomyocytes changed in a concentration-dependent manner when incubating with lidocaine. The higher the concentration, the more significant the inhibition of lidocaine on cardiomyocytes. CONCLUSlON The cardiotoxicity of quinidine and lidocaine can be detected accurately using RTCA Cardio system, suggesting that this system can be used in early evaluation of drug cardiotoxicity.