ECG Analysis in Anesthetized Mice

All mice were intraperitoneally tranquilized with diazepam (20 mg/Kg) and the transducers were carefully placed subcutaneously according to chosen preferential derivation (DII). The traces were recorded during 2 minutes using a digital system Power Lab 2/20 that was connected to a bio-amplifier at 2 mV for 1 s (PanLab Instruments, Barcelona, Spain). Filters were standardized to between 0.1 and 100 Hz and traces were analyzed using the Scope software for Windows V3.6.10 (PanLab Instruments, Barcelona, Spain). We measured the heart rate (beats per minute, bpm), the duration of the P wave and QRS, ad PR and QT intervals in milliseconds (ms). The relationship between the QT interval and the RR interval in the mouse was assessed in all animals. To obtain physiologically relevant values for the heart rate-corrected QT interval (QTc) in units of time (rather than time to a power that is not equal to 1), the observed RR interval (RR0) was first expressed as a unitless multiple of 100 ms, yielding a normalized RR interval, RR100 = RR0/100 ms. Next, the value of the exponent (y) in the relationship QT0 = QTc×RRy100 was assessed, with QT0 indicating the observed QT (in ms) and the unit for QTc being milliseconds. The natural logarithm was computed for each side of this relationship [(QT0) = In (QTc)+yln (RR100)]. Thus, the slope of the linear relationship between the log-transformed QT and RR100 defined the exponent to which the RR interval ratio should be raised to correct QT for heart rate [7] (link).