ECG Research

ECG waves, telemetry ecg lead placement, ecg data, ecg database, cardiac monitor lead placement, ecg signal database

An electrocardiogram (ECG or EKG) is a measure of how the electrical activity of the heart changes over time as action potentials propagate throughout the heart during each cardiac cycle. As the heart beats, membrane polarity changes in the electrical conduction system throughout the heart result in the depolarization and repolarization of the atrial and ventricular cardiac cells, causing them to contract and relax. This results in the chambers pumping blood throughout the body.  This contraction (depolarization) and relaxation (repolarization) can be measured using electrodes placed in different combinations and configurations on the chest and limbs to produce a series of ECG complexes. An ECG complex is comprised of different components, or waves, that represent the electrical activity in specific regions of the heart.

ECG Cycle Breakdown:

  • P Wave – represents the movement of an electrical wave originating at the sinoatrial (SA) node and resulting in the depolarization of the left and right atria.
  • P-R Segment – the pause in electrical activity caused by a delay in conduction of the electrical current at the atrioventricular (AV) node to allow blood to flow from the atria to the ventricles before ventricular contraction occurs.
  • P-R Interval – the time between the beginning of atrial depolarization and the beginning of ventricle depolarization. A change in P-R interval is often an indicator of the activity of the parasympathetic nervous system on the heart.
  • QRS Complex – represents the electrical activity from the beginning of the Q wave to the end of the S wave and the complete depolarization of the ventricles, leading to ventricular contraction and ejection of blood into the aorta and pulmonary arteries
  • S-T Segment – the pause in electrical activity after the complete depolarization of the ventricles to allow blood to flow out of the ventricles before ventricular relaxation begins and the heart fills for the next contraction.
  • S-T Interval – the time between the end of ventricular depolarization (S wave) and the end of repolarization (T wave end).
  • Q-T Interval – the time between the beginning of the ventricular depolarization (Q wave) and the end of repolarization (T wave end).
  • T Wave – represents the repolarization of the ventricles.

Note: The repolarization of the atrial chambers is obscured by the depolarization of the ventricles and is thus not specifically represented within the ECG complex.

 

ECG Solutions from DSI

DSI offers a variety of solutions for studies requiring ECG endpoints from restrained or freely moving animal models. DSI has developed robust ECG solutions for data acquisition and analysis from signals that were acquired via implantable telemetry, external telemetry, or hardwired methods. Available monitoring solutions cover small to large animal models and offer researchers the ability to collect one or many physiological signals. DSI’s ECG solutions offer flexibility, reliable performance and quality to satisfy your research needs.
Typically, the ECG is measured from the surface of the body by placing two electrodes directly on the skin and reading the potential difference between them. The detected waveform features depend on the amount of cardiac tissue involved in the contraction, as well as the orientation of the electrode placement with respect to the heart. A number of different ECG lead configurations exist based on electrode location and configuration.

Two types of leads may be recorded:

  • Bipolar – measures the potential difference between two electrodes on either side of the heart (e.g. limb leads I, II, III).
  • Unipolar – measures the potential difference between a single electrode and a reference potential obtained by averaging the potentials at other lead sites. This includes the augmented limb leads (aVR, aVL, and aVF) and the precordial leads (V1-10).

Combinations of these lead types comprise the cardiac monitoring lead systems most commonly used in pre-clinical physiologic monitoring.

  • 2-electrode, 1-lead system
    Lead II is the most commonly collected and analyzed ECG lead and is the recommended lead position for telemetry applications because it normally produces the largest positive R wave. Electrodes are typically placed at the Right Arm (RA) and Left Leg (LL) positions, but this depends on the animal model used (see Implantable Telemetry below). Lead II is sufficient for monitoring heart rate change, R-wave detection, and ventricular fibrillation, but is less sensitive than multi-lead systems.

  • 4-electrode, 6-lead system
    The 4-electrode, 6-lead system is the basic configuration used for measuring ECG’s, and the building block from which the other lead systems build (described below). The 6-lead system is measured by placing electrodes at the left arm (LA), right arm (RA), left leg (LL), and right leg (RL) locations. Using this configuration, the bipolar limb leads (I, II, and III) and unipolar augmented limb leads (aVR, aVL, and aVF) can be obtained. Advantages to the 6-lead system include greater sensitivity to arrhythmia monitoring and the addition of timing, channel, and dispersion information across multiple ECG leads. Lead II is the most commonly used lead, and the recommended lead position for telemetry applications, because it normally produces the largest positive R wave. Lead II is sufficient for monitoring heart rate change, R-wave detection, and ventricular fibrillation, but is less sensitive than systems that derive more leads.

  • 8-electrode, 10-Lead System
    The 10-lead system is typically used in veterinary and research environments. Electrode placement for a 10-lead system is identical to that of the 6-lead system with the addition of four precordial electrodes. The precordial leads are used to obtain a three dimensional view of the heart’s electrical activity since the heart does not sit flat in the chest, especially in canines. Placement of the four precordial electrodes in a 10-lead system depends on the species used (see Hardwired Solutions below). 10-lead systems result in the following recording leads: limb leads I, II, III, augmented leads aVR, aVL, aVF, and 4 precordial leads. It is important to note that in research applications, such as Safety Pharmacology and Toxicology, a subset of the 10-lead system is typically used with electrode configurations dependent on the species used and study protocol definition. Typical ECG leads evaluated in these types of studies are leads I, II, aVF, V1, and V2 as they reliably provide a clearly defined P-wave, QRS complex, and T-wave. The addition of the precordial chest leads will usually result in the best combination of a clear P-wave and T-wave, which is important for Q-T prolongation.

  • 10-electrode, 12-lead System
    The 12-lead system is used in human clinical cardiology and adds 2 additional electrodes to record the following ECG leads: limb leads I, II, III, augmented limb leads aVR, aVL, aVF, and precordial leads V1-V6. This system is not normally used in preclinical physiologic research.

Implantable Telemetry

Small Animal

A single lead (2 electrode system) ECG is typically collected when using PhysioTel™ implantable telemetry with small animal models. DSI recommends using a modified lead II position for electrode placement to obtain a strong ECG signal with clear morphologies (see Figure 1). Since the device is implanted, the lead wires are tunneled subcutaneously to the desired electrode positions and secured to the muscle using sutures.


Large Animal

The small animal recommendation is also applicable for large animal models. However, with large animal telemetry, DSI also provides an alternative approach using our Solid Tip ECG lead which has been proven to provide accurate ECG signals while virtually eliminating muscle noise and artifact. When using the Solid Tip lead, the positive lead can be placed in a variety of different locations including the abdominal side of the diaphragm, the epicardium, or subcutaneously. However, the negative electrode (Solid Tip electrode) is inserted into the right jugular vein and advanced until the desired ECG morphology is obtained – the tip will be positioned in the superior/cranial vena cava. See Figure 2 for an example.

Note: Lead II electrode placement for swine is different than other large animal species due to the orientation of their heart (see Figure 3). DSI recommends a modified lead II placement – base/apex – for high quality ECG recordings.

 

 

Surgical Support

Please contact DSI Surgical Services for surgical support, guides, and videos for detailed procedures on ECG lead placement.

External Telemetry

The Jacketed External Telemetry (JET™) devices use standard ECG skin electrodes. There are 3 different models of JET devices, each differing in the number of ECG leads that can be acquired per device.
 

JET-EA-BP JET-3ETA-BP JET-5ETA-BP

# ECG leads available per device

1 7 9

Table 1: Available ECG leads by JET device
 

The color coding for the provided 3 Channel ECG lead set is based on the Association for the Advancement of Medical Instrumentation (AAMI) standards. The following table outlines where the colored leads would be placed on an animal.

 

Location

AAMI (US, Japan)

Left Arm (LA)

Black

Right Arm (RA)

White

Left Leg (LL)

Red

Right Leg (RL)

Green

Chest Lead or V lead (Vx)

Brown

Table 2: AAMI standar electrode coloring and associated placement locations
   

The preferred electrode placement on a canine is presented in Figure 4. The electrodes are close together on the front of the chest and abdomen in locations comparable to implantable Modified Lead II electrode placement (see Implantable Telemetry section).  Please note that it is recommended to place electrodes over bone to minimize signal artifact due to muscle activity. This placement has an advantage in that if respirationbands are used they will not rest overtop the electrodes.

 


 
Figure 4: Preferred JET electrode placement in canine model (left). Alternative electrode placement approach (right).
 

 

For non-human primate ECG lead placement, it is recommended to start with previously defined standard electrode placement locations.  Modifications to support jacketed data collection may be necessary in order to minimize muscle artifact and/or allow for proper instrumentation. Some researchers recommend the electrode placement presented in Figure 5. In general the arm electrodes are placed on the clavicle and the leg electrodes are placed on the bottom of the rib cage (still over bone). The V-lead is considered a chest lead and is typically placed in one of ten locations. 

 

 

 Figure 5: Example of JET 5-electrode, 7-lead placement for non-human primate model.

 

Hardwired Solutions

Hardwired solutions are commonly used in toxicology settings to measure traditional snap-shot ECG’s using 8-electrode, 10-Lead systems. It is important to note that based on the study protocol a subset of the 10-lead system is typically used for data acquisition and based on the ECG morphology, a subsection of those leads acquired would be assessed.

For canine models, leads I, II, III, aVR, aVL, aVF, V2, V4, and V10 are commonly acquired, while ECG analysis is typically based only on leads I, II, aVF, V2, and V4. Figure 6 represents the precordial lead placement for canine models.     

For non-human primates models, leads I, II, III, aVR, aVL, aVF, V1, V2, and V3 are typically acquired, while ECG analysis is based only on leads I, II, aVF, V1, and V2. Typically the V1 electrode is placed at the right fourth intercostal space, the V2 electrode is placed at the left fourth intercostal space, and the V3 electrode is placed at the left mid-axillary line in the fifth intercostal space. Note: the V10 dorsal electrode is not typically used for primate models. Figure 7 represents the typical electrode placement used for this model.     

ECG electrode placement for swine models differ due to the orientation of their heart in the chest. To obtain optimal measurements, the four ECG electrodes are placed to capture the base-apex cardiac vector using the Nehb-Soerri axial system to obtain the limb leads I, II, and III and the augmented leads aVL, aVF, and aVR.  The following are the electrode placements for this approach: the left leg (LL) electrode is placed at the apex of the heart in the intercostal space between the fifth and sixth rib, the right leg (RL) electrode is placed at the proximal 1/3 of the right fore leg, the right arm (RA) is placed at the right mastoid process, and the left arm (LA) is placed proximal of the sacrum (see Figure 8).  

Data Acquisition Software

DSI offers Ponemah™ software to help researchers facilitate acquisition of their ECG data. 

If researchers prefer to acquire their data in a 3rd party system, DSI offers analog output solutions for the majority of our ECG implants.


Data Analysis Software

After data acquisition has taken place, DSI’s Ponemah™ software can be used to efficiently analyze ECG data sets using attribute-based analysis or our ECG Pattern Recognition Option (ECG PRO)

  • Standard attribute-based analysis can analyze a single lead or perform cross-lead comparisons with superior noise detection and elimination in real-time and post-acquisition.
  • ECG PRO greatly reduces post-processing time via template-based analysis as it allows the selection of a template cardiac cycle for precise comparisons to other cycles in the data set.

The following list identifies the parameters that can be calculated using Ponemah’s standard attribute-based and ECG PRO analysis modules:

  • Intervals
    Heart Rate, R-R Interval, S-T Interval, QRS Width (Duration), P-R Interval, Q-T Interval, Q Alpha T Negative, Q-R Interval, QATN Interval, Pwave Width, Twave Peak to Twave End Interval
  • Amplitudes
    Rwave Height, Pwave Height, Twave Height, Twave Negative Height, Variable S-T Elevation, Q-R Amplitude, Rwave +dV/dt Maximum, Twave Area, Twave Peak, Noise
  • Corrected Values
    Corrected Q-T Interval - Bazett, Fridericia, Van de Water, Matsunaga, and King methods
  • Counts
    Pwave, Twave, Q-T Interval, Rwave, Bad waves, Good waves, Total waves
  • Multi-lead ECG Cross Channel Calculations
    Timing, Channel, and Dispersion Information Across Multiple Leads, Q-T Dispersion
  • Cross Channel Calculations
    Q-A Interval (requires Systemic Blood Pressure signal), Electromechanical Widow (requires Left Ventricular Pressure signal)
  • Percent Match via ECG PRO
    % Match, % Pwave Match, % Qwave Match, % Swave Match, % Twave Match
Each of DSI’s solutions for ECG research consist of the recommended sensors, hardware, software, and accessories needed to reliably and accurately collect and analyze your data.

DSI provides all of the necessary components for a complete ECG monitoring solution.  Each recommended system consists of the necessary telemetry implant, hardware, software, and accessories.  Please note that there is flexibility in the number of animals that can be monitored on a single system and the following solutions can be adapted to meet your study needs.

Implantable Telemetry


DSI’s PhysioTel™ implants are designed for monitoring and collecting data from conscious, freely moving laboratory animals—providing stress-free data collection while eliminating percutaneous infections. PhysioTel implants are offered in different sizes to support a variety of research models ranging from mice and rats to dogs and non-human primates.

The PhysioTel Digital System is the newest and most advanced system for large animal models offering group-housing capability, while the PhysioTel System is our basic system for large and small animal models and does not allow for group housing.

DSI offers a variety of implant models to help researchers optimize data collection and simplify studies. 

Species

Biopotential Channel Count

1

2

3

4

XS (Mouse)

ETA-F10, ETA-F20, EA-F20, HD-X11

F20-EET

SA (Rat, Guinea Pig)

CA-F40, CTA-F40, HD-S11, HD-S21

F40-EET

F50-EEE

4ET

LA (Dog, NHP)

CTA-D70, D70-PCT, D70-PCTP, D70-PCTR,

L21, L11

D70-CCTP

D70-EEE

 Table 1: PhysioTel implant model by species and biopotential channel count

PhysioTel Systems include:

*Only required if implant contains a pressure channel

PhysioTel System_SA_MX2

PhysioTel Digital Systems include:

*Only required if implant contains a pressure channel


PhysioTel Digital System_LA

Analog Output to 3rd Part Systems include:

PhysioTel System_Analog

External Telemetry

External telemetry is a non-invasive method offering continuous ECG measurements through surface electrodes using DSI’s Large Animal Jacketed External Telemetry (JET). Common applications for JET include toxicology studies where implantable telemetry may be inappropriate or cost prohibitive, but still require continuous ECG recordings. Respiratory and Blood Pressure endpoints can also be collected using JET.

JET Systems include:

*Blood Pressure Add-On requires the Ambient Pressure Reference (APR-1) and E2S-1.


JET System

Hardwired Monitoring Systems

DSI offers two hardwired ECG options suitable for use in repeat dose toxicology studies. The Multi-lead ECG Pod is able to provide 12-lead ECG presentations from a standard industry 10-electrode patient cable. The Isolate/Defibrillation Protected ECG and General Purpose Probes are able to provide a single ECG presentation.

DSI's new bibliography search tool may help you find publications known to use DSI technology. It is searchable by keyword, title and author and references of interest can be easily exported. The following publications have been included as references to demonstrate how ECG endpoints can be acquired from restrained or freely moving animal models and applied to specific research applications.

Small Animal

Sgoifo, A., et al., “Electrode positioning for reliable telemetry ECG recordings during social stress in unrestrained rats.” Physiology and Behavior. 1996 Mar; 60(6):1397-1401.

London, B., “Cardiac arrhythmias: From (transgenic) mice to men.” J Cardiovascular Electrophysiology. 2001 Sep; 12(9):1089-1091.

Hess, P.,Rey, M., Wanner, D., Steiner, B., Clozel, M., “Measurements of blood pressure and electrocardiogram in conscious freely moving guineapigs: a model for screening QT interval prolongation effects.” Laboratory Animals. 2007 Jan; 41:470-480.

Petric, Clasen, van Weßel, et al., “In vivo electrophysiological characterication of TASK-1 deficient mice.” Cellular Physiology and Biochemistry. 2012.

Large Animal

Hamlin, R. “How many ECG leads are required for in vivo studies in safety pharmacology.” J of Pharmacological and Toxicological Methods. 2008; 57:161-168.

Holzgrefe, H., Cavero, I., Gleason, C., Warner, W., Buchanan, L., Gill, M., Burkett, D., Durham, S., “Novel probabilistic method for precisely correcting the QT interval for heart rate in telemetered dogs and cynomolgus monkeys.” J of Pharmocological and Toxicological Methods. 2006.

Stubhan, M., Markert, M., Mayer, K., et al., “Evaluation of cardiovascular and ECG parameters in normal, freely moving Göttingen minipig.” ­ J Phamacological and Toxicological Methods. 2008 Feb; 57:202-211.

Authier S, Moon LB, Stonerook M, Fournier S, Gervais J, Maghezzi S, Troncy E. “Evaluation of a novel ECG lead placement method in telemetered freely moving cynomolgus monkeys: assessment of an intravascular biopotential lead.” J Phamacological and Toxicological Methods. 2011 Sep-Oct; 64(2):145-150.

Cools, F., et al., “ECG arrhythmias in non-implanted vs. telemetry-implanted dogs: Need for screening before and sufficient recovery time after implantation.” J Pharmacological and Toxicological Methods. 2011.
 
Prior, H., McMahon, N., Schofield, J., Valentin, J., “Non-invasive telemetric electrocardiogram assessment in conscious beagle dogs.” J Pharmacological and Toxicological Methods. 2009 Jun; 60:167-173.