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Arrhythmia Research



What is an Arrhythmia?
An arrhythmia occurs when the electrical impulses that coordinate heart rhythm are not working properly. This can lead to abnormal heart rhythms, causing the heart to beat too fast, too slow or irregularly. 
Why Measure Arrhythmias?

Arrhythmias occur spontaneously in normal, healthy animals at a low incidence. Many arrhythmias are not harmful and have no clinical significance; however, some may have more serious effects and lead to cardiac arrest or sudden death. Changes in the incidence rate or type of arrhythmia may indicate disease progression or treatment effect. The underlying pathophysiology of arrhythmias is complex and still not fully understood. Animal models ranging from mice to pigs are frequently used in arrhythmia research, with dogs and primates being two of the most commonly used in treatment evaluations. 


The tables below shows the most prevalent arrhythmias in the beagle dog and the cynomolgus monkey. Both the dog and the cynomolgus monkey can have prevalent occurrences of sinus rhythms to include bradycardia, tachycardia, sinus arrhythmia and premature ventricular complexes. 

Incidence/prevalence of spontaneous arrhythmia: beagle dog1

Dog Arrhythmias

Incidence/prevalence of spontaneous arrhythmia: cynomolgus monkey1

Monkey Arrhythmias




Factors that can Cause Arrhythmias
  • Cardiac diseases
  • Electrolyte imbalances
  • Cardiomyopathy
  • Injury from myocardial infarction
  • Healing post cardiac surgery
  • Smoking
  • Drug abuse
  • Stress or anxiety
  • Medications
  • Genetics



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The Most Common Arrythmia Types1
Common Arrhythmias


How are Arrhythmias Measured?
Arrhythmias are identified by looking at an electrocardiogram (ECG) signal and assessing the rate and regularity of the heartbeat. Typically, ECG is measured 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, and 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. DSI offers several technologies to record ECG,  including implantable telemetry, external telemetry or hardwired options. 


Implantable Telemetry 


 

DSI implants are designed for monitoring and collecting data from conscious, freely moving animals.  Implants are offered in different sizes to support a variety of animal species including mice, rats, dogs and non-human primates. Several telemetry models are capable of monitoring ECG and blood pressure.

 


Hardwired Signals


 

Short durations of functional endpoints are collected non-invasively from chemically or physically restrained animals that are connected to external  devices capable of monitoring surface ECG or blood pressure and recording  directly into an acquisition and analysis computer system.

 


Jacketed External Telemetry

JET system

 

ECG and blood pressure signals are collected from conscious, freely moving animals wearing a jacket which contains and protects a small JET device capable of monitoring cardiovascular data and transmitting data to an acquisition and analysis computer system.

 

1150 Arrhythmia articles citing DSI in Google Scholar




Arrhythmia Detection and Analysis

Traditional arrhythmia detection is accomplished by examining ECG waveforms to assess heart rate and rhythm. Anomalies are found by manually counting the number of normal complexes (p waves for atrial rate, QRS for ventricular) in a given time period, looking for variations in waveform morphology, and marking missing waveforms. Until recently with the release of Data Insights, previously developed software made only marginal improvements in this process.

Data Insights
Unlock the information in your data.


Data Insights™ offers an automated analysis method to accurately and consistently find, classify, and report on the arrhythmias within the ECG signal. The following table outlines the arrhythmia types, classifications, and quantification parameters available with Data Insights.

Types of Arrhythmias Classifications Reporting Parameters
Ventricular beats Runs of complexes Durations
Atrial beats Couplets Occurrences
Junctional beats Triplets Cycles per occurrence
Atrioventricular (AV) block Bigeminy Distribution
Sinus pause Trigeminy
Premature beats





 




DSI's 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 arrhythmias can be assessed and data applied to specific research applications.

References

Small Animal

Adeyemi, O., Parker, N., Pointon, A., & Rolf, M. (2020). A pharmacological characterization of electrocardiogram PR and QRS intervals in conscious telemetered rats. Journal of pharmacological and toxicological methods, 102, 106679.

Chowdhury, R. A., Debney, M. T., Protti, A., Handa, B. S., Patel, K. H., Lyon, A. R., ... & Peters, N. S. (2021). Rotigaptide Infusion for the First 7 Days After Myocardial Infarction–Reperfusion Reduced Late Complexity of Myocardial Architecture of the Healing Border‐Zone and Arrhythmia Inducibility. Journal of the American Heart Association, 10(9), e020006.

Hayes, A. W., Pressman, P., Moser, P., & Soares-da-Silva, P. (2020). Regulatory safety pharmacology evaluation of BIA 10-2474. Journal of pharmacological and toxicological methods, 102, 106677.

Hayter, E. A., Wehrens, S. M., Van Dongen, H. P., Stangherlin, A., Gaddameedhi, S., Crooks, E., ... & Bechtold, D. A. (2021). Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia. Nature communications, 12(1), 1-13.

Lebsir, D., Cantabella, E., Cohen, D., Sache, A., Ebrahimian, T., Kereselidze, D., ... & Souidi, M. (2020). Effect of repetitive potassium iodide on thyroid and cardiovascular functions in elderly rats. Biochemistry and Biophysics Reports, 24, 100816.

Paterek, Aleksandra, Barbara Sochanowicz, Marta Oknińska, Witold Śmigielski, Marcin Kruszewski, Urszula Mackiewicz, Michał Mączewski, and Przemysław Leszek. "Ivabradine prevents deleterious effects of dopamine therapy in heart failure: No role for HCN4 overexpression." Biomedicine & Pharmacotherapy 136 (2021): 111250.

Pecha, S., Yorgan, K., Röhl, M., Geertz, B., Hansen, A., Weinberger, F., ... & Schwoerer, A. P. (2019). Human iPS cell-derived engineered heart tissue does not affect ventricular arrhythmias in a guinea pig cryo-injury model. Scientific reports, 9(1), 1-12.


Large Animal 

1Gauvin, D.V., Tilley, L. P., Smith, F. W. K. Jr., Theodore J. Baird. (2009). Spontaneous cardiac arrhythmias recorded in three experimentally- and drug-naive laboratory species (canine, primate, swine) during standard pre-study screening. Journal of Pharmacological and Toxicological Methods. 59(2) 57-61. doi: 10.1016/j.vascn.2008.12.001

Baublits, J., Vargas, H. M., & Engwall, M. J. (2021). The in vivo QTc core assay: An evaluation of QTc variability, detection sensitivity and implications for the improvement of conscious dog and non-human primate telemetry studies. Journal of Pharmacological and Toxicological Methods, 109, 107067.

Chui, R. W., Derakhchan, K. & Vargas, H. M. (2012). Comprehensive analysis of cardiac arrhythmias in telemetered cynomolgus monkeys over a 6 month period. Journal of Pharmacological and Toxicological Methods. 66(2):84-91. doi: 10.1016/j.vascn.2012.05.002

Cools, F., & Gallacher, D. (2009). Normal prevalence of cardiac arrhythmias in 24 h ECG recordings of chronically telemetered, healthy, freely moving beagle dogs. Journal of Pharmacological and Toxicological Methods, 60(2), 235–236. http://doi.org/10.1016/j.vascn.2009.04.112

Freudenberger, T., Kranz, B., Lehmann, W., Schäfer, K., Münter, K., Lee, K., ... & Hucker, W. J. (2021). Identification of two preclinical canine models of atrial fibrillation to facilitate drug discovery. Heart rhythm, 18(4), 632-640.

Honda, M., Komatsu, R., Holzgrefe, H. H., Yamada, Y., Isobe, T., Kimura, K., ... & Tabo, M. (2010). Application of probabilistic analysis for precisely correcting the QT interval for heart rate in telemetered common marmosets. Journal of pharmacological and toxicological methods, 61(3), 264-270.

Tilley, L. P., Smith, F. W. K., Oyama, M. A., & Sleeper, M. M. (2008). Manual of Canine and Feline Cardiology (Fourth Edition). Elsevier.



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