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Cell culture Fingolimod medium was replaced once daily. Usually, drug therapy was begun 60?80 h after cell seeding determined by seeding density. Data collection is controlled by a computer software that operates the hardware and allows an individual to define the sampling frequency and sampling window. Sampling frequency is defined as the number of times all through an experimental run the beating is felt and the window is defined as the period of time that the beating is clearly measured. For instance, if the sampling frequency is sampling window and 15 min is for 5 s, it indicates that all 15 min the machine will Microelectronic monitoring of practical cardiotoxicity BJP British Journal of Pharmacology 165 1424?1441 1425 record beating information for 5 s. In a typical experiment, before compound treatment, the sampling frequency is after every hour and the window is 20 s. 5 minutes before therapy, the cells are sampled every minute for 20 s to establish standard recording. After therapy, the sampling frequency is every minute for the first hour, every 5 min for the 2nd hour Metastatic carcinoma and every 15 min for 3?24 h. The sample window for every recording is set at 20 s. After the data-acquisition, the RTCA Cardio application is used to calculate the parameters such as beating rate, amplitude, beating period, normalized beating rate, normalized amplitude, and beating flow irregularity index and provide future basic statistical data, such as mean and SD and to calculate EC50 values for dose response assessment. Definition of terms and analysis parameters Each assessed beating period refers to the excitationcontraction coupling of the cardiomyocytes. Aurora Kinase Inhibitor The conventional measured beating design is illustrated in Figure 2C. The beatings are comprised of a sequence of good peaks and negative peaks. The Cell Index difference between one negative peak for the following positive peak is defined as amplitude. The time between each positive peak means beating period and the beating rate is calculated based on each beating period to derive how many beats occurred per minute. Three time relevant parameters, decay time Td, rise time Tr, and half plethora widthTIBD50, handle the temporal beating feature. For data analysis, the related variables are determined for every beating within one recording period, and the mean and SD are derived correspondingly. To be able to compare the result of tested substances, beating rate or amplitude after compound treatment are normalized to once place before treatment to acquire the normalized beating rate or normalized amplitude. In order to evaluate the degree of arrhythmia, the BRI list is derived according to the coefficient of variation of the beating period during one record period.