Name: Real-Time Electrocardiogram Monitoring During Treadmill Training in Mice (Video) | JoVE Journal
Uploaded: 2022-05-05T15:00:00.000+00:00
Duration: 4 min 45 s
Description: Learn real-time ECG monitoring during treadmill training in mice to study exercise-induced cardiac arrhythmias. This method enables precise electrophysiological assessment in transgenic models for inherited syndromes.

ai_agent_IP

ai_agent

maintenance

instantTrialDurationMinutes

isBiopharma

enableNewMyJoveSectionDesign

educationFeatures

seoMetaApi

ai_copilot_institution_blacklist

ai_chat_institution_blacklist

freeAccessWindow

ssoRoleCapture

scheduledMaintenanceBanner

joveLabsFeatures

disable_autoplay_for_bots

extended_trial_duration

5 minutes

This work was supported by the German Research Foundation (DFG; Clinician Scientist Program in Vascular Medicine (PRIME), MA 2186/14-1 to P. Tomsits), the German Centre for Cardiovascular Research (DZHK; 81X2600255 to S. Clauss), the Corona Foundation (S199/10079/2019 to S. Clauss), and the ERA-NET on Cardiovascular Diseases (ERA-CVD; 01KL1910 to S. Clauss). The funders had no role in manuscript preparation.

The authors have nothing to disclose.

Current guidelines recommend regular physical activity as it has been demonstrated to be an important modifier of cardiovascular risk factors30. There is also a growing body of evidence that moderate physical activity may protect against atrial fibrillation (AF) both in primary and secondary prevention31,32,33. On the contrary, endurance athletes such as marathon runners have a higher risk to develop AF i...

Regular physical activity is important for a healthy life. Certain cardiovascular conditions, however, lead to situations where this common-sense agreement is at least questionable. In patients with myocarditis, current data even shows adverse effects of exercise and, thus, it is recommended to pause all exercise for a certain period in these patients1,2,3. In other cardiovascular diseases (CVD) such as inherited arrhythmia syndromes comparatively less evidence on the appropriate level of exercise exists4,5,6,7, making clinical counselling in these cases, mostly for young and physically active patients, very challenging.
Adverse remodeling leading to reduced contractility and heart failure and proarrhythmogenic remodeling leading to arrhythmias and sudden cardiac death have been suggested as hallmarks of exercise-associated harmful effects on the heart8. A large number of studies indicate beneficial effects of moderate exercise over a broad spectrum of different diseases9,10. Extensive training, however, may have detrimental effects on the heart leading to arrhythmias especially in otherwise healthy athletes11. Although structural remodeling processes leading to a vulnerable proarrhythmic substrate production may underlie this paradox situation as demonstrated in marathon runners12, the specific mechanisms of exercise-related adverse remodeling both in healthy people and in patients with cardiovascular diseases remain largely unknown.
In animals, especially in mice, several suitable models have been developed to mimic a broad range of cardiovascular diseases13,14. Also, various exercise models and training protocols have been established in mice15,16,17, including motorized treadmill training, voluntary wheel running (VWR), and swimming17,18. Evaluation of cardiac electrophysiology by ECG monitoring classically depends on a direct conducting connection between the animal and some sort of detection device. Thus, either animals need to be anesthetized, e.g., to obtain ECG recordings using sharp electrodes19, or animals need to be immobilized by a restrainer 20, or data quality is reduced due to motion artifacts, e.g., when using paw-electrodes21 or conductive platforms22 allowing only basic analysis. Thus, none of the above-mentioned approaches are compatible with training protocols and consequently prevent studies on exercise-related mechanisms leading to adverse remodeling in mice. Implantable telemetry devices can overcome these hurdles and are nowadays the most powerful tool and gold standard to evaluate murine electrophysiology in vivo in conscious and moving animals23,24. Current telemetry hardware solutions have been developed to monitor mice in their cages25,26,&#160;and commonly require a receiver to be placed underneath the cage for data acquisition, thus making real-time monitoring outside these circumstances challenging. Here we provide an approach to investigate the effects of exercise on cardiac electrophysiology and arrhythmogenesis by real-time ECG recording during treadmill training in mice using implanted telemetry devices. All parameters obtained were analyzed as previously described by Tomsits et al.23.

<table><tbody><tr><td>14-gauge needle</td><td>Sterican</td><td>584125</td><td></td></tr><tr><td>Any mouse</td><td>e.g. Jackson Laboratories</td><td></td><td></td></tr><tr><td>Bepanthen</td><td>Bayer</td><td>1578675</td><td></td></tr><tr><td>Carprofen 0.005 mg/&amp;micro;L</td><td>Zoetis</td><td>53716-49-7</td><td></td></tr><tr><td>Data Exchange Matrix 2.0 (MX2)</td><td>Data Science International</td><td></td><td>Manages communication between PhysioTel and PhysioTel HD telemetry implants and the acquisition computer.</td></tr><tr><td>Enrofloxacin 25 mg/ml</td><td>Baytril</td><td>400614.00.00</td><td></td></tr><tr><td>Fentanyl 0.5 mg/10 mL</td><td>Braun Melsungen</td><td></td><td></td></tr><tr><td>Fine forceps</td><td>Fine Science Tools</td><td>11295-51</td><td></td></tr><tr><td>Five Lane Treadmill for Mouse</td><td>Panlab - Harvard Apparatus</td><td>76-0896</td><td>Includes treadmill unit, touchscreen control unit, a sponge , and cables</td></tr><tr><td>Iris scissors</td><td>Fine Science Tools</td><td>14084-08</td><td></td></tr><tr><td>Isoflurane 1 mL/mL</td><td>Cp-Pharma</td><td>31303</td><td></td></tr><tr><td>Isoflurane vaporizer system</td><td>Hugo Sachs Elektronik</td><td>34-0458, 34-1030, 73-4911, 34-0415, 73-4910</td><td>Includes an induction chamber, a gas evacuation unit and charcoal filters</td></tr><tr><td>LabChart Pro 8.1.16</td><td>ADInstruments</td><td></td><td></td></tr><tr><td>Magnet</td><td>Data Science International</td><td></td><td></td></tr><tr><td>Modified Bain circuit</td><td>Hugo Sachs Elektronik</td><td>73-4860</td><td>Includes an anesthesia mask for mice</td></tr><tr><td>Modular connectors</td><td>Data Science International</td><td></td><td>Connecting cables between Reciever, Signal Interface and Matrix 2.0 (MX2)</td></tr><tr><td>Novafil s 5-0</td><td>Medtrocin/Covidien</td><td>88864555-23</td><td></td></tr><tr><td>Octal BioAmp</td><td>ADInstruments</td><td>FE238-0239</td><td>Amplifier for recording Surface ECG</td></tr><tr><td>Octenisept</td><td>Sch&amp;uuml;lke</td><td>121418</td><td></td></tr><tr><td>Oxygen 5 L</td><td>Linde</td><td>2020175</td><td>Includes a pressure regulator</td></tr><tr><td>PhysioTel ETA-F10 transmitter</td><td>Data Science International</td><td></td><td></td></tr><tr><td>PhysioTel receiver RPC-1</td><td>Data Science International</td><td></td><td>Signal reciever</td></tr><tr><td>Ponemah 6.42</td><td>Data Science International</td><td></td><td>ECG Analysis Software</td></tr><tr><td>Powerlab</td><td>ADInstruments</td><td>3516-1277</td><td>Suface ECG Acquisition hardware device. Includes ECG electrode leads</td></tr><tr><td>Prism 8.0.1</td><td>Graph Pad</td><td></td><td></td></tr><tr><td>Radio Device (Sony AF/AM)</td><td>Sony</td><td></td><td></td></tr><tr><td>Signal Interface</td><td>Data Science International</td><td></td><td>Acquires and synchronizes digital signals with telemetry data in Ponemah v6.x.</td></tr><tr><td>Spring scissors</td><td>Fine Science Tools</td><td>91500-09</td><td></td></tr><tr><td>Surgical platform</td><td>Kent Scientific</td><td>SURGI-M</td><td></td></tr><tr><td>Tergazyme 1%</td><td>Alconox</td><td>13051.0</td><td>Commercial cleaning solution</td></tr><tr><td>Tweezers</td><td>Kent Scientific</td><td>INS600098-2</td><td></td></tr></tbody></table>

real-time electrocardiogram monitoring during treadmill training in mice

Real-Time Electrocardiogram Monitoring During Treadmill Training in Mice

Regular physical exercise is a major contributor to cardiovascular health, influencing various metabolic as well as electrophysiological processes. However, in certain cardiac diseases such as inherited arrhythmia syndromes, e.g., arrhythmogenic cardiomyopathy (ACM) or myocarditis, physical exercise may have negative effects on the heart leading to a proarrhythmogenic substrate production. Currently, the underlying molecular mechanisms of exercise-related proarrhythmogenic remodeling are largely unknown, thus it remains unclear which frequency, duration, and intensity of exercise can be considered safe in the context of disease(s).
The proposed method allows to study proarrhythmic/antiarrhythmic effects of physical exercise by combining treadmill training with real-time monitoring of the ECG. Implantable telemetry devices are used to continuously record the ECG of freely moving mice over a period of up to 3 months both at rest and during treadmill training. Data acquisition software with its analysis modules is used to analyze basic ECG parameters such as heart rate, P wave duration, PR interval, QRS interval, or QT duration at rest, during and after training. Furthermore, heart rate variability (HRV) parameters and occurrence of arrhythmias are evaluated. In brief, this manuscript describes a step-by-step approach to experimentally explore exercise induced effects on cardiac electrophysiology, including potential proarrhythmogenic remodeling in mouse models.

Depending on individual research objectives, subsequent analysis of obtained telemetry data will differ widely. Here, we demonstrate feasibility of the method by obtaining good quality data recorded during training periods and provide exemplary results of ECGs and heart rate variability analyses before, during, and after training. Data are presented as mean ± standard error of mean (SEM), all statistical analyses were conducted with a suitable statistical software (see Table of Materials). Statistical si...

Electrocardiogram (ECG) is the key variable to understanding cardiac electrophysiology. Physical exercise has beneficial effects but may also be harmful in the context of cardiovascular diseases. This manuscript provides a method of recording real-time ECG during exercise, which can serve to investigate its effects on cardiac electrophysiology in mice.

Regular physical exercise is a major contributor to cardiovascular health, influencing various metabolic as well as electrophysiological processes. ...

real-time-electrocardiogram-monitoring-during-treadmill-training

Research

JoVE Journal

Medicine

Programmed electrical stimulation provides the ability to determine conduction properties of the heart, and the possibility to induce and terminate cardiac arrhythmias using various pacing protocols. Using a transvenous catheter, intracardiac electrogram recordings can be obtained in mice following programmed electrical stimulation protocols to identify arrhythmogenic substrates.

Programmed Electrical Stimulation in Mice

Transthoracic echocardiography offers a noninvasive method for the evaluation of cardiac function in mice. A combination of ultrasound and Doppler imaging modalities can be used to obtain dimensional measurements of the heart and intracardiac blood flow, which together provide an assessment of cardiac systolic and diastolic performance.

Transthoracic Echocardiography in Mice

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.

Ambulatory ECG Recording in Mice

A surgical technique for implantation of commercially available telemetry transmitters used for continuous measurement of biopotential (one-lead ECG), heart rate, core body temperature and locomotor activity in freely moving mice is shown. Recommendations and protocols for post-operative care and pain relief, improving recovery, well being and survival rate are also presented.

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

We describe the protocol to perform a cardiac stress test induced by dobutamine and monitored by cardiac catheterization in normal mice. Also we show its application to unmask subclinical cardiac disease in high fat diet-induced obese mice.

Cardiac Stress Test Induced by Dobutamine and Monitored by Cardiac Catheterization in Mice

During murine myocardial ischemia/reperfusion surgery, correct placement of the occluding ligature is typically confirmed by visible observation of myocardial pallor. Herein, a method of electrocardiographically confirming ischemia and reperfusion, to supplement observed myocardial pallor, is demonstrated in male C57Bl/6 mice.

Confirmation of Myocardial Ischemia and Reperfusion Injury in Mice Using Surface Pad Electrocardiography

Here, we present a protocol to record brain and heart bio signals in mice using simultaneous video, electroencephalography (EEG), and electrocardiography (ECG). We also describe methods to analyze the resulting EEG-ECG recordings for seizures, EEG spectral power, cardiac function, and heart rate variability.

Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy

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.

Electrocardiogram Recordings in Anesthetized Mice using Lead II

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

We present a novel approach to quantify nanoparticle localization in the vasculature of human xenografted tumors using dynamic, real-time intravital imaging in an avian embryo model.

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Learn real-time ECG monitoring during treadmill training in mice to study exercise-induced cardiac arrhythmias. This method enables precise electrophysiological assessment in transgenic models for inherited syndromes.

Real-Time Electrocardiogram Monitoring During Treadmill Training in Mice

Explore More Videos