Real-Time Electrocardiogram Monitoring During Treadmill Training in Mice

Podsumowanie

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.

Streszczenie

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.

Wprowadzenie

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 patients^1,2,3. In other cardiovascular diseases (CVD) such as inherited arrhythmia syndromes comparatively less evidence on the appropriate level of exercise exists^4,5,

Protokół

All animal procedures were conducted in accordance with the guidelines of the Animal Care and Ethics committee of the University of Munich and all procedures were approved by the Government of Bavaria, Munich, Germany (ROB-55.2-2532.Vet_02-16-200). Four male wildtype in-house bred C57BL/6N mice were used in this study.

1. Preparation and surgical implantation of the transmitter

NOTE: For a detailed protocol of transmitter preparation and implantation refer to McCauley et al.²⁶.

1. Preparation of the transmitter
   1. Use new transmitters directly as these ar....

Wyniki

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). Statistic.......

Dyskusje

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 prevention^31,32,33. On the contrary, endurance athletes such as marathon runners have a higher risk to develop AF i.......

Materiały

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