Ambulatory ECG Recording in Mice
May 27th, 2010
Telemetric ECG has emerged as an essential tool in evaluating animal models for cardiac arrhythmias and sudden cardiac death. Here, we present a stepwise guide to telemetric ECG recordings for application in long-term ambulatory ECG monitoring in mice.
Beacon surgery by shaving the mouse, placing it under anesthesia and sterilizing the abdomen and chest at the planned operative site, make a vertical midline incision in the abdomen with a scalpel exposing the peritoneum. Make another vertical midline incision in the peritoneum for insertion of the telemeter. Insert the TER in the right abdomen underneath the peritoneum, leaving only the leads exposed.
So the peritoneum closed subcutaneously implant TER leads such that the negative or white lead is implanted in the upper right chest and the positive or red lead is implanted over the left upper abdomen. Finally close the skin with sutures. Hi, I'm Mark McCauley from the laboratory of Xandr Wearan in the Department of Medicine at Baylor College of Medicine.
Today I'll be showing you a technique for implanting ECG TERs in mice. We use this technique to study changes in heart rate and heart rhythm and mice. So let's get started.
Before inserting an ECG TER into the mouse, it is important to make sure the TER is sterile and in good working order. This is an example of a small animal telemeter from Data Sciences International with a red positive lead and a white negative lead. Each lead has an insulating sheath, two millimeters of exposed wire, and a plastic capped tip, which prevents erosion of the lead through the skin.
New telemetry devices are typically provided in a sterile condition by the manufacturer, but TERs can be reused provided air cleaned using zyme, 1%solution for over four hours. Additionally, use WA OFI O one disinfectant overnight to sterilize the ECG Telemeter. Be sure to wash the disinfectant off with sterile water before implantation into mice.
Check the telemeter leads for integrity of both the conducting wires and the insulating sheath. Turn on the telemetry transmitter using a magnet and test the signal with an AM radio frequency five 30. The signal should be strong and clear and should vary in intensity and pitch based on manipulation of the wires.
Record the model number, the TER serial number, and the ECG calibration value. If applicable, manufacturers often recommend that the TER should be on for 24 hours prior to implantation. Refer to the instruction manual for your specific ter.
To prepare the TER lead, cut the negative or white lead to approximately 3.5 centimeters and the positive or red lead to 2.5 centimeters. These are the optimal lengths per implantation of the negative lead in the right chest and the positive lead in the left abdomen. Next, remove the insulating sheath to expose seven millimeters of wire.
Paint the ends of the metal lead with super glue and then attach lead caps to the metal tips. These caps will avoid skin erosion due to lead placement. Approximately two to three millimeters of the metal wire should be exposed for electrical sensing of the native heart rhythm.
The use of sterile techniques is crucial in the surgery. For implantation of the telemeter, you will need sterile gloves, a sterile drape, and six O proline sutures. All surgical instruments should be sterilized in a glass bead sterilizer heated to 250 degrees Celsius.
These include two pairs of forceps, one pair of blunt ended scissors, a scalpel, and a needle driver. Be sure to sterilize and wash the TER as previously described before. Use to prepare the mouse for surgery.
First anesthetize the animal in an induction box. After confirming by a toe pinch that the mouse is adequately sedated, completely shave the abdomen and chest of the mouse with electric clippers. Re anesthetize the mouse with isof fluorine and then transfer the mouse to a constant flow anesthesia tube.
Place it in the supine position with its head facing away and tail towards you. Tape down the pause of the mouse to the heated surgical table. Use a heating pad to maintain the temperature of the anesthetized animal within a narrow range of 37 plus or minus one degree Celsius.
A rectal probe may be used to monitor the temperature, wipe its abdomen with an alcohol swab to remove shaved hair and to clean the operative field. Apply Betadine with swabs three times to disinfect the abdomen and chest. Apply the sterile drape to the abdomen of the mouse for intraperitoneal toter implantation.
Begin by using a scalpel to create a vertical midline incision of about 2.5 centimeters in length in the skin, overlying the abdomen using blunt tended scissors. Carefully separate skin from underlying connective tissues. Then create a vertical midline incision in the linear elbow, overlying the peritoneum roughly 1.5 centimeters in length.
Additionally, create a small hole in the peritoneum, just cranial to the peritoneal incision, which will serve as an outlet for subcutaneous leads. While performing surgery, keep the surgical site moist, occasionally dripping sterile saline onto the operative site. Insert the TER into the right peritoneal cavity.
Insert forceps into the hole, superior to the TER, and pull both leads up through the lead hole such that they are protruding from the peritoneum. Use continuous six oh proline sutures to close the 1.5 centimeter peritoneal vertical midline incision. To place the ECG leads in the lead two configuration.
The negative lead with the white transparent sheath will be placed in the right thoracic area. First, create a 0.5 centimeter skin incision in the mouse's upper right chest. Next, use the blunt scissors to create a tunnel back to the abdominal incision.
Pull the negative lead through the tunnel and use a six oh prolene suture to anchor the lead to the pectoral muscle. Make sure the suture is on top of the exposed part of the lead and creates a good contact between the exposed metal wire and underlying muscle. Use a second suture proximal to the previous one to immobilize the lead to the muscle.
Close the skin incision using two three proline sutures. The positive lead is placed in the left abdomen below the left diaphragm and below the heart. An additional incision is not necessary here because the site of lead implantation is close to the vertical midline incision.
Use a six oh proline suture to anchor the lead to the underlying abdominal muscle, making sure it has good contact with the tissue. Finally, close the abdominal muscle and skin sequentially with six O proline sutures in layers. Provide the mouse with the appropriate postoperative care as described in our protocol text.
Now we will show some representative results of a normal ECG waveform. The normal ECG from a wild type mouse clearly shows a P wave, which represents atrial depolarization, followed by a QRS wave, which represents ventricular depolarization. Notice that the p and QRS waves are distinct from the small background noise and that each P wave precedes each QRS in a one-to-one ratio.
Notice also that the distance between each R wave called the R to R interval and between each P wave called the sinus cycle length is regular to noting that the mouse is in normal sinus rhythm. So we've just shown you how to implant an ECG TER into a mouse for ambulatory ECG recording. When performing this procedure, it's important to adequately clean the TER before insertion to place the leaves in the appropriate positions, to completely close the abdomen, and finally to give appropriate analgesia to the mouse after the procedure.
So that's it. Thanks for watching and good luck with your experiments.
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Overview
This article presents a stepwise guide to telemetric ECG recordings for long-term ambulatory ECG monitoring in mice. Telemetric ECG is crucial for evaluating animal models of cardiac arrhythmias and sudden cardiac death.
Key Study Components
Area of Science
- Cardiac electrophysiology
- Animal models
- Telemetric monitoring
Background
- Cardiac arrhythmias pose significant risks in animal models.
- Sudden cardiac death is a critical area of research.
- Telemetric ECG provides continuous monitoring capabilities.
- Understanding cardiac function in mice is essential for translational research.
Purpose of Study
- To provide a detailed methodology for telemetric ECG in mice.
- To enhance the understanding of cardiac events in animal models.
- To facilitate research on cardiac arrhythmias and sudden cardiac death.
Methods Used
- Shaving and anesthetizing the mouse.
- Surgical implantation of a telemeter in the abdomen.
- Placement of ECG leads in specific anatomical locations.
- Closure of the surgical site with sutures.
Main Results
- Successful implantation of telemetric ECG devices.
- Effective long-term monitoring of cardiac activity.
- Demonstration of the procedure's feasibility in mice.
- Potential applications in studying cardiac health and disease.
Conclusions
- Telemetric ECG is a valuable tool for cardiac research.
- The methodology can be applied to various studies in mice.
- Further research can enhance understanding of cardiac arrhythmias.
Frequently Asked Questions
Executive Industry Relevance
Ambulatory ECG telemetry in mice enables continuous, long-term monitoring of cardiac electrophysiology, which is essential for de-risking arrhythmia mechanisms and sudden cardiac death phenotypes in preclinical models. This approach supports target validation by providing quantitative, reproducible heart rate and rhythm data that bridge discovery to translational cardiology programs. Scalable multi-animal recording enhances throughput for lead identification and predictive safety screening in cardiovascular drug discovery pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by capturing spontaneous arrhythmias and conduction abnormalities in freely moving mice over weeks to months.
- Operational Value: Provides longitudinal heart rate variability and QT interval data to functionally validate ion channel or structural targets implicated in cardiac safety.
Screening & Assay Development
- Scientific Value: Generates standardized, noise-resistant ECG waveforms (P wave, QRS complex) for automated interval measurement and arrhythmia detection assays.
- Operational Value: Supports assay reproducibility through sterile telemetry preparation, lead fixation protocols, and preoperative validation of signal integrity using AM radio frequency testing.
Translational & Preclinical Research
- Scientific Value: Facilitates disease-relevant system modeling by enabling detection of rare arrhythmic episodes and sinus cycle length variations that mirror human cardiac electrophysiology.
- Operational Value: Ensures translational continuity from discovery through preclinical validation via consistent lead placement (Einthoven’s II configuration) and postoperative monitoring protocols.
Pipeline & Workflow Integration
This method integrates into the cardiovascular discovery continuum from target hypothesis testing through lead optimization to preclinical safety assessment, providing ambulatory phenotyping that informs go/no-go decisions.
- Discovery Biology: Supports mechanistic de-risking by isolating cardiac electrophysiology variables in conscious, ambulatory mice, reducing confounding from anesthesia or restraint.
- Screening: Enables scalable, simultaneous multi-animal recording for high-content screening of compound effects on heart rate variability and arrhythmia burden.
- Analytics: Delivers quantitative dependent variables including R-to-R interval, sinus cycle length, P-wave morphology, and QRS duration for statistical comparison across genotypes or treatment groups.
- Translational Research: Aligns with preclinical continuity by modeling human-relevant cardiac conduction parameters and enabling longitudinal safety pharmacology studies.
- Enterprise Reuse: Establishes a reusable telemetry platform for chronic cardiac monitoring across multiple indication areas (e.g., heart failure, channelopathies) within centralized core facilities.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in target validation by reducing mechanistic ambiguity through direct, long-term electrogram sensing in physiologically relevant states.
- Operational Value: Enhances standardization and reproducibility via aseptic technique requirements, lead length specifications (3.5 cm negative, 2.5 cm positive), and suture-based fixation protocols.
- Strategic Value: Improves capital efficiency by enabling rare event capture (e.g., ventricular tachycardia) that would otherwise require impractical surface ECG sampling frequencies.
- Portfolio Impact: Supports risk-adjusted advancement decisions by providing objective arrhythmia incidence and heart rate variability metrics for cardiovascular liability assessment.
Implementation Considerations
- Requires expertise in rodent sterile surgery, including peritoneal incision, subcutaneous lead tunneling, and muscle-anchored suture techniques.
- Dependent on telemetry hardware infrastructure (transmitters, receivers, AM radio frequency validation tools) and sterile processing capabilities (glass bead sterilizer, enzymatic cleaning, disinfectant protocols).
- Necessitates cross-team standardization between surgery, animal care, and data analysis groups to ensure consistent lead placement (white lead upper right chest, red lead left upper abdomen) and signal quality thresholds.
- Involves adaptation considerations for different mouse strains or disease models where lead positioning may require adjustment based on thoracic anatomy or body mass index.
- Includes practical limitations such as lead erosion risk mitigated by plastic-capped tips and postoperative analgesia requirements for animal welfare compliance.
