ecgTUNNEL: Non-invasive ECG and respiration on conscious rodents

 

Combining surface ECG monitoring and respiration by plethysmography, ecgTUNNEL is a plug-and-play system for snapshot ECG recordings and respiration data in rodents that eliminates the need for surgery and anesthesia. 

It allows you to avoid complications or adverse side effects encountered with the use of anesthesia, implantation, or at-risk/fragile models, favoring experiments that comply with the 3R’s and IACUC (Institutional Animal Care and Use Committee ) protocols.

High throughput screening for phenotyping, model development, disease progression, drug effects, etc. allows for efficient and cost-effective assessment of large cohorts.

 

Kimberly Londer BS works at the BioMET Center, in the University of Maryland. She is using ecgTUNNEL to capture ECG on young mice.

Read the interview

 

ecgTUNNEL-rat+Dome

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The methodology used by ecgTUNNEL for more than 10 years, has proved successful1 and is now used in a variety of applications.

1 Non-invasive restrained ECG recording in conscious small rodents: a new tool for cardiac electrical activity

 

HIGHLIGHT ON RECENT STUDIES:

 

Emery-Dreifuss muscular dystrophy

Muscular-distrophy-2EDMD (Emery-Dreifuss muscular dystrophy) is characterized by muscle weakness and cardiomyopathy.

In the study conducted by Nicolas Vignier et al2, genetic background and how it may influence the phenotype has been investigated, using various mouse strains.

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Various physiological parameters were characterized, including:

  • Body weight loss
  • Decreased survival time
  • Increased left ventricular end systolic diameter
  • Decreased fractional shortening
  • PR interval and QRS complex duration extended
  • RR interval prolongation
  • Increases susceptibility to arrhythmia

Cardiac structure and function were determined by echocardiograph while ECG intervals and arrhythmia were assessed using the ecgTUNNEL.

2 Effect of genetic background on the cardiac phenotype in a mouse model of Emery-Dreifuss muscular dystrophy - Nicolas Vignier et al, Biochemistry and Biophysics Reports, September 2019

Hutchinson-Gilford Progeria Syndrome

HGPS-2Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disease characterized by premature aging and accompanied by severe cardiovascular disorders.

Gabriel Balmus’ team has worked on the NAT10 enzyme, showing that its inhibition with Remodelin might offer an additional therapeutic opportunity to improve patient’s lifespan.

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A mouse model that exhibits premature-aging phenotypes was used for this experiment. Data highlighted how Remodelin treatment delayed the onset of cardiovascular pathologies that represent the most debilitating aspect of HGPS. Heart measurements were collected over the different week intervals, using the ecgTUNNEL.

Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Balmus G, Nat Commun, 2018

Pediatric cardiac research

pediatric-cardiology_Plan de travail 1

This study assesses cardiac electrophysiology and calcium handling throughout postnatal development, using both in vivo and whole heart models.

 

 

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In this experiment, Luther M Swift et al used Sprague-Dawley rats from postnatal day 0 to adulthood. In vivo surface ECG were collected with ecgTUNNEL continuously for 2 minutes while ex vivo measurements were performed on a Langendorff perfusion system.

Cardiac electrophysiology changes and calcium handling within the first week after birth were characterized and can serve for future pharmacological and toxicological assessments.

Age-dependent changes in electrophysiology and calcium handling implications for pediatric cardiac research - Luther M. Swift et al, Am J Physiol Heart Circ Physiol. 2019

E-cigarette exposure

e-cigs and vapes-ecgtunnel

This experiment was designed to evaluate heart rate, heart rate variability and blood pressure of mice exposed to E-cigarette vapor containing nicotine, which represents more than 99% of e-cigarettes marketed.

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Scireq inExpose system was used to expose mice for 60 minutes daily to freshly made e-cigarette vapor for 3 months.

Non-invasive blood pressure and electrocardiograms were recording each week during sessions of a few minutes. ecgTUNNEL was used to measure HR and HRV in 15 minutes intervals both pre-exposure and post-exposure.

Obtained data led Ashley Du’ team to suggest that chronic inhalation of nicotine containing e-cigarette vapor affects cardiac function.

Cardiac Effects of Daily Inhalation of E-cigarette Vapor. Ashley Du et al, 2019

Meet the expert

 

KIMBERLY LONDER BS

from the University of Maryland, Baltimore

Kimberly Londer BS works at the BioMET Center, in the University of Maryland. She is multi-focal and works with the orthopedic department and as a cardiac research assistant. She is using ecgTUNNEL to capture ECG on young mice, without anesthesia.

We are pleased to share an interview with Kimberly, who kindly shared her thoughts about her research with us.

 

INTERVIEW:

 

Q: What interest you the most about your research ?

A: I am very interested in how daily aspects of life, i.e. diet, sleep, and exercise affect the heart and implications of heart disease with age. I was drawn to this type of research from an artistic background. I enjoy creating/designing models and some of the newest heart treatments include 3D printed clamps and valves that assist with atrial and/or ventricular function. 

 

Q: What does the general landscape of this research area currently look like ?

A: Much of the research involved in heart disease is focused on the role of calcium movement in and out of cells and how mitochondrial changes, whether genetic/congenital, or as a result of injury, can alter heart function.

 

Q: What are the real-world implications of your research?

A: The use of emka’s non-invasive ecgTUNNEL allows me to phenotype animals for various heart conditions. With this information, the BioMET research team is developing treatment options for a double transgenic mouse model with atrial fibrillation (AF). It is hoped that these treatments could be developed further for use in human patients suffering from AF.

 

Q: How long have you been an emka TECHNOLOGIES user? 

A: About 6 months.

 

Q: How has using ecgTUNNEL helped with improving the translatability and reproducibility of your research?

A: Using ecgTUNNEL has been more-so groundbreaking rather than “improving” as there is few systems, publications, or data that exists on small animal ECG without the use of anesthesia or telemetry. The data captured from the ECG is easily reproducible with an appropriate acclimation period within the ecgTUNNEL prior to recording. The recordings are very clean with minimal smoothing and filtering.

 

Q: What were some insights that emka equipment has helped you obtain?

A: emka equipment has helped our research lab compile data of heart rates, R-R rates, QT lengths, and more in animals that are unanesthetized and without telemetry implants. This feature of emka’s equipment eliminates issues associated with other methods like lowered heart rate and increased stress.

 

Q: What other measurements are taken alongside ECG, and why?

A: Outside of using ECG parameters, heart tissue is analyzed for hypertrophy, fibrosis, mitochondrial function and calcium levels. Some of the mice are also put on an echocardiogram. These studies are performed to further the understanding of the mechanisms that perpetuate AF.

 

Q: What features of the equipment or software do you find most useful?

A: Being able to have a library of waves which you can label yourself is very helpful. It allows me to scan an entire recording for AF, ventricular disorders and other arrhythmias of interest within seconds. The different options for smoothing and wave detection are great. I enjoy being able to compare the raw data to the filtered data within the same window on the ecgAUTO program.

 

Q: What was the reasoning behind selecting your animal model?

A: We use a model of mouse that, with appropriate breeding scheme, is born with AF with symptoms manifesting as early as 2 months old. We are using this model in a series of AF experiments.

 

Q: What advice do you have for someone starting out in this research area?

A: Due to the limited research involving the true shape of the mouse ECG, I would recommend additional research outside of a regular ECG course. Mouse heart waves are different than humans due to the increased heart rate which results in the lack of a plateau phase and a “J” wave at the end of the QRS complex. This difference must be accounted for when comparing research data of mice to that of clinical data from human patients.

 

Q: What’s next for your lab and your research?  

A: I will continue to use the ECG to positively phenotype the mice for AF and other arrhythmias. Within the next months, we plan to administer different drugs in hopes of reducing or eliminating the burden of AF in the mice.

 

Q: Any specific recommendations, to finish with?
A: When putting animal in, it’s easiest to have head restraint as far back as possible. Put animal in and immediately tighten side knob so that tunnel cannot move (Mice are strong enough to push top tunnel off if not done immediately) THEN, adjust head and rear restraints to desired location. Some of my calmer mice don’t even get restrained anymore, they just walk right in, and take a nap. I do always adjust rear restraint so they cannot back out but I often do not have to use head restraint. I would also recommend to:

  • . Put animal in ecgTUNNEL and let sit for a few moments once or twice before actual recording begins. (2-5 min/day, a day or so prior to recording).
  • . Record in a dim/dark room with limited noise or cover tunnel.
  • . Use electrode gel, readings come out much clearer than without.
  • . Watch for moving hands and feet! Often times, the mice push their back legs out of the whole where their tail is supposed to come.
         Give them a little tickle with a pen tip to get them to readjust their footing.
  • . Keep cages of mice away from those on tunnel. Sounds and smells of cage mates are distracting!

 

THANK YOU, Mrs LONDER, FOR THIS INTERVIEW!

 

If you have any questions about the use of ecgTUNNEL, please contact us!

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