The significance of our protocol is that the electrocardiogram measurement can be performed with great sensitivity in a small mouse that has been manipulated genetically or pharmacologically. The protocol is advantageous in that it is simple, fast, inexpensive, and sensitive. Additionally, it can be performed on small mice, even neonates.
We believe that this method would contribute to the understanding of unexplored regions of arrhythmia in the cardiovascular area. Demonstrating the procedure will be Tae Woong Ha from my laboratory. Begin by opening the analysis software and setting it up for ECG data acquisition.
Go to Setup and Channel Settings and set the Sample Rate to 2, 000 samples per second. Set the range to 20 millivolts and the input amplifier to 200 Hertz of low pass. Next, go to ECG Analysis and ECG Settings, then choose Mouse in the Preset of Detection and Analysis Settings.
In the Averaging panel, choose to concatenate and consecutive cardiac cycles into a single average signal or averaging view and a table view. In the QTc panel, select the Bazett method, which is defined as the heart rate corrected value of QT interval. Place the mouse on the precision scale and record its weight.
After ensuring that the mouse is properly anesthetized insert electrodes with acupuncture needles into the right and left forelimbs and the left hindlimb. Make sure that electrode depth and position are consistent throughout the experiments. Connect the other ends of the electrodes by clicking them into the three snap connectors at the other end of the lead wires of the three lead bio amplifier cable and inject drugs approximately three minutes after the anesthetics.
10 minutes after administering anesthetics, begin recording the ECG. Once the recording is completed, use the ECG data from 12 to 17 minutes after injection of anesthetics for analysis. When finished, carefully remove the electrodes.
To determine whether this noninvasive ECG measurement reflects the influence of autonomic modulation on the cardiac conduction system, normal BALB/c mice were challenged with agonists and antagonists of the autonomic nervous system. Compared to vehicle control, heart rate increased significantly in atropine and isoprenaline treated mice and fell with carbachol. In addition, the QTc interval rose in atropine and isoprenaline treated mice and decreased in carbachol treated mice.
Representative chart views and averaging views of the ECG signals in atropine, carbachol and vehicle treated mice are shown here. When attempting this protocol, the most important thing is to ensure that the ECG electrodes are securely inserted throughout the experiment. Perform multiple preliminary experiments until the ECG signals are stable and consistent.
Our previous publications with mice confirmed ECG variations that had been reported in human genetic studies, which supports the utility of this method in cardiovascular research areas such as arrhythmia.