How can ECG recording in rats be more profitable for preclinical research?

By Raafat Fares, PhD

The heart role in the organism

The pacemaker cells located in the heart generate electrical impulses that travel through the heart. This electrical signal leads to the contraction of cardiac muscles and to blood pumping throughout the body via a network of vessels. The circulating blood provides cells with oxygen and nutrients and helps dispose of metabolic wastes. This cardiovascular system (heart, blood, vessels) is essential in maintaining life and thus its monitoring is of utmost importance.

The electrocardiogram (ECG): a valuable tool to monitor the heart electrical activity and detect potential drugs candidate effects

The ECG is a test that measures the cardiac electrical activity and provides relevant information in clinical assessments of cardiovascular health and in the diagnosis of heart disease. ECG was shown to be acutely sensitive to the toxic effects of chemicals and drugs. In addition, it enables the detection of cardiac arrythmias with drugs acting on cardiac ion-channels.

ECG similarities in rats and humans

Despite some differences in cardiac anatomy and electrophysiology, there are essential similarities between rat and human ECG [1]. For this reason, ECG in rats has been exploited in basic cardiovascular research investigating heart’s performance under physiological conditions and in animal models of cardiovascular diseases.

ECG recording in rats: overview of currently available techniques

While there are recommendations for the standardization, recording and interpretation of the human ECG [2], it is not the case for the rat. This lack of recommendation left the door wide open for improvisation and innovation. Indeed, several invasive and non-invasive techniques were developed allowing 1 to 12 channel ECG recordings [3] [4]. Most studies used limb lead II for the general analysis of ECG parameters in rodents [5], whereas precordial leads were used for localization of pathological processes such as myocardial ischemia [6].

• Invasive ECG recording in rats

Implantable telemetry is the gold standard invasive ECG recording technique [5]. Telemetry implants as well as electrodes are implanted at different locations after a surgery. After a recovery period, data from transmitters are gathered wirelessly by a receiver positioned outside the rat cage enabling measurements in freely moving rats for several weeks.

• Non-invasive ECG recording in restrained rats

Non-invasive ECG techniques are used either in restrained or in freely moving rat. In restrained model, conscious rats are placed in a restrainer (referred as a tunnel) in which the paws are positioned on ECG sensors embedded in the tunnel floor. After an adaptation period, up to 6 lead ECG can be recorded up to 60 minutes [7].

• Non-invasive ECG recording in freely moving rats: Innovative jacket monitoring technique

A freely moving rat that wears DECRO jacket

Rat dressed with the DECRO jacket

 

In freely moving, it consists of dressing rats with a jacket under which two external ECG electrodes are placed on the skin surface.

These electrodes are connected to a telemetry transmitter that is placed under or within the jacket layers and data are wirelessly transmitted to the receiver. In the majority of cases, the jacket is used as a physical tool to support and maintain the electrodes and the transmitter.

However, recently the role of the jacket was upgraded to become more than just a supporting tool but a functional respiratory recording tool. Respiratory inductive plethysmography was integrated via thoracic and abdominal plethysmographic sensors embedded within the jacket [8].

Due to the interaction between cardiovascular and respiratory systems, the recording of ECG in association with respiration can have large advantages and applications in the preclinical research field.

If you want to know more or if you have a case to discuss, don’t hesitate to contact us at corinne.simon@etisense.com

or visit www.decro.fr

Related articles : 

[1] A. K. Farraj, M. S. Hazari, et W. E. Cascio, « The Utility of the Small Rodent Electrocardiogram in Toxicology », Toxicological Sciences, vol. 121, no 1, p. 11‑30, mai 2011, doi: 10.1093/toxsci/kfr021.

[2] P. Kligfield et al., « Recommendations for the Standardization and Interpretation of the Electrocardiogram: Part I: The Electrocardiogram and Its Technology: A Scientific Statement From the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology », Circulation, vol. 115, no 10, p. 1306‑1324, mars 2007, doi: 10.1161/CIRCULATIONAHA.106.180200.

[3] P. Konopelski et M. Ufnal, « Electrocardiography in Rats: a Comparison to Human », Physiol Res, p. 717‑725, oct. 2016, doi: 10.33549/physiolres.933270.

[4] P. P. Pereira-Junior, M. Marocolo, F. P. Rodrigues, E. Medei, et J. H. M. Nascimento, « Noninvasive method for electrocardiogram recording in conscious rats: feasibility for heart rate variability analysis », An. Acad. Bras. Ciênc., vol. 82, no 2, p. 431‑437, juin 2010, doi: 10.1590/S0001-37652010000200019.

[5] M. Tontodonati, N. Fasdelli, et R. Dorigatti, « An improved method of electrode placement in configuration Lead II for the reliable ECG recording by telemetry in the conscious rat », Journal of Pharmacological and Toxicological Methods, vol. 63, no 1, p. 1‑6, janv. 2011, doi: 10.1016/j.vascn.2010.03.001.

[6] P. Krenek et al., « Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function », European Journal of Heart Failure, vol. 11, no 2, p. 140‑146, févr. 2009, doi: 10.1093/eurjhf/hfn026.

[7] H. Mongue-Din, A. Salmon, M. Y. Fiszman, et Y. Fromes, « Non-invasive restrained ECG recording in conscious small rodents: a new tool for cardiac electrical activity investigation », Pflugers Arch – Eur J Physiol, vol. 454, no 1, p. 165‑171, mars 2007, doi: 10.1007/s00424-006-0197-8.

[8] T. FLENET, H. BARRET, E. CHASTEL, A. MOMTAZ, C. EYNARD, et C. BOIXEL, « ASSESSMENT OF CARDIORESPIRATORY FUNCTION USING TELEMETRIC JACKET IN RODENTS », présenté à SAFETY PHARMACOLOGY SOCIETY ANNUAL MEETING, Barcelone, 26/09 2019.