RESUMO
Aim To establish an in vitro arrhythmia detection technique based on real-time cell analysis (RTCA) Cardio sys-tem with aconitine as a tool drug, and to provide a reliable method for the development of antiarrhythmic drugs. Methods The effects of aconitine on rat cardiac rhythm were detected by eight-channel physiological recorder at the level of whole animal. In vitro cultured cardiac myocytes, the inoculation density of cardiac myocytes was investigated by HTCA method, the effect of aconitine on cardiac beating was monitored by RTCA Cardio system, and the CI value, beating rate, amplitude and irregular rhythm of cardiac myocytes were analyzed. Results Eight-channel physiological recorder was used to detect the effects of aconitine on whole animals. The results showed that aconitine(50 mg • g"1) could induce arrhythmias such as ventricular tachycardia, ventricular fibrillation, shortened RR interval and increased heart rate. RTCA Cardio system showed that aconitine (2-8 p,M) could induce arrhythmias such as increased cardiac cell beating frequency, decreased beating amplitude and abnormal beating state in a dose-dependent manner. Conclusions RTCA Cardio system can rapidly, sensitively and accurately detect the arrhythmia induced by aconitine in cardiac myocytes, which provides methodological reference for the development of antiarrhythmic drugs.
RESUMO
Aim To establish an in vitro early drug cardiac tox-icity evaluation method by human embryonic stem cells derived cardiomyocytes ( hESC-CM) and real-time cell analysis Cardio (RTCA Cardio) system. Method The hESC-CM were cultured at RTCA Cardio E-Plate 96. Impedance signals from hESC-CM were analyzed for beating rate, contraction amplitude and beating rhythm irregularity to determine the optimum inoculation density and detection duration. Based on this, we used 0. 1 % DMSO to be the solvent and quinidine (0. 2, 0. 78, 3. 13, 12. 5, 50 and 100 μmol·L - 1 ) known as affecting cardiac activity to validate this method. Result The results revealed no significant changes in the cell index (CI), transient pulse patterns, beating rate and amplitude of hESC-CM. Quinidine will affect the CI and transi-ent pulse patterns of hESC-CM and decrease the beating rate and amplitude of hESC-CM when its concentration ≥3. 13 μmol · L - 1 . And this effect is concentration-dependent, the higher the concentration,the more time they need to recover beating and the more significant the beating rate and amplitude inhibition of quinidine on hESC-CM. Conclusion The method established by hESC-CM and RTCA Cardio system can detect the effect of quinidine on the contraction of hESC-CM, and this indicates that this method has the potential to be an attractive high-throughput tool for screening potential drugs in early evaluation of drug car-diotoxicity.