Electrocardiogram Recordings in Anesthetized Mice using Lead II
June 20th, 2020
We present an ECG protocol that is technically easy, inexpensive, fast, and affordable in small mice, and can be performed with enhanced sensitivity. We suggest this method as a screening approach for studying pharmacological agents, genetic modifications, and disease models in mice.
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.
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Overview
This article presents a simple and cost-effective ECG protocol for small mice, including neonates, that enhances sensitivity in measurements. The method is proposed as a valuable screening tool for pharmacological studies and genetic modifications.
Key Study Components
Area of Science
- Electrophysiology
- Cardiovascular research
- Pharmacology
Background
- Electrocardiogram (ECG) measurements are crucial for understanding cardiac function.
- Existing methods may lack sensitivity in small animal models.
- Genetic and pharmacological manipulations can affect cardiac physiology.
- There is a need for accessible and efficient protocols for small mice.
Purpose of Study
- To develop an ECG protocol that is easy to implement and cost-effective.
- To enhance the sensitivity of ECG measurements in small mice.
- To provide a screening method for various pharmacological and genetic studies.
Methods Used
- Setup of analysis software for ECG data acquisition.
- Application of the protocol on genetically or pharmacologically manipulated mice.
- Measurement of ECG with a focus on sensitivity.
- Demonstration of the procedure by a trained laboratory member.
Main Results
- The protocol allows for sensitive ECG measurements in small mice.
- It is simple, fast, and inexpensive compared to existing methods.
- Potential to explore previously unexamined areas of arrhythmia.
- Applicable to both adult and neonatal mice.
Conclusions
- This ECG protocol is a significant advancement for cardiovascular research in small animal models.
- It facilitates the study of pharmacological agents and genetic modifications.
- The method can contribute to a deeper understanding of cardiac arrhythmias.
Frequently Asked Questions
Executive Industry Relevance
This ECG protocol enables sensitive, low-cost cardiac phenotyping in genetically or pharmacologically manipulated mice, supporting early target validation in cardiovascular drug discovery. By providing reliable heart rate and QTc interval measurements in anesthetized models, it enhances predictive confidence for autonomic modulation studies and reduces technical barriers in preclinical safety screening. The method is particularly valuable for de-risking mechanistic hypotheses in arrhythmia research and facilitating go/no-go decisions in lead optimization.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of autonomic nervous system effects on cardiac conduction through agonist/antivantagonist challenge studies.
- Operational Value: Provides reproducible heart rate and QTc interval readouts for functional target validation in murine models.
- Predictive Value: Supports mechanistic de-risking by detecting expected ECG changes with atropine, carbachol, and isoprenaline, aligning with established pharmacological responses.
Screening & Assay Development
- Assay Readiness: Delivers standardized ECG acquisition with 2,000 Hz sampling rate and Bazett-corrected QTc for consistent quantitative outputs.
- Scalability: Enables high-sensitivity screening in small and neonatal mice, expanding usable models for early cardiotoxicity assessment.
- Workflow Integration: Supports reproducible compound evaluation through stable electrode placement and defined 12–17 minute post-anesthetic analysis window.
Translational & Preclinical Research
- Disease Relevance: Facilitates exploration of arrhythmia mechanisms in genetic models, bridging findings from human genetic studies to murine systems.
- Translational Continuity: Enables longitudinal cardiac monitoring from discovery through preclinical validation using consistent ECG parameters.
- Risk-Adjusted Advancement: Improves confidence in pharmacological studies by detecting autonomic-mediated ECG changes that correlate with known compound effects.
Pipeline & Workflow Integration
The method fits within the discovery continuum from target hypothesis testing to lead identification, providing electrophysiological readouts that inform early cardiovascular pharmacology and safety profiling.
- Discovery Biology: Supports pathway clarification by measuring heart rate and QT correction changes in response to autonomic modulators.
- Screening: Enables assay-ready, reproducible ECG measurements in murine models for compound effect evaluation.
- Analytics: Generates quantitative heart rate and QTc interval data using Bazett correction for cross-condition comparison.
- Translational Research: Connects murine ECG responses to human arrhythmia research through validated pharmacological profiles.
- Enterprise Reuse: Establishes a reusable, low-cost ECG platform for repeated use across genetic and pharmacological screening campaigns.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in target validation by reducing mechanistic ambiguity in cardiac conduction studies.
- Operational Value: Delivers standardization, reproducibility, and scalability through simple electrode setup and defined acquisition parameters.
- Strategic Value: Improves go/no-go decisions by enabling sensitive detection of compound-induced ECG changes in early studies.
- Portfolio Impact: Supports risk-adjusted prioritization by identifying cardiologically active compounds through autonomic response profiling.
Implementation Considerations
- Requires expertise in murine anesthesia, electrode placement, and ECG software configuration.
- Dependent on bio amplifier hardware capable of 2,000 Hz sampling and 20 mV range settings.
- Necessitates standardization across teams for electrode depth, lead placement, and anesthetic timing.
- Adaptation considerations include model-specific electrode size and weight-based dosing for neonatal versus adult mice.
- Practical limitations include anesthesia-induced physiological changes that may affect baseline ECG parameters.
