The present work describes an experimental protocol of transesophageal atrial burst pacing for efficient induction of atrial fibrillation (AF) in rats. The protocol can be used in rats with healthy or remodeled hearts, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of new therapeutic strategies.
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Method Article
Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats
In This Article
Summary
Abstract
Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. Reentry, one of the main mechanisms involved in AF pathogenesis, requires a certain mass of myocardial tissue in order to occur. Due to the small size of the atria, rodents have long been considered 'resistant' to AF. Although spontaneous AF has been shown to occur in rats, long-term follow-up (up to 50 weeks) is required for the arrhythmia to occur in those models. The present work describes an experimental protocol of transesophageal atrial burst pacing for rapid and efficient induction of AF in rats. The protocol can be successfully used in rats with healthy or remodeled hearts, in the presence of a wide variety of risk factors, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of novel prophylactic and/or therapeutic strategies.
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice and its incidence and prevalence continue to increase dramatically worldwide1. This arrhythmia affects up to 4% of the world population according to recent studies2. However, given that paroxysmal AF can be asymptomatic and may therefore escape detection, the true prevalence of AF is likely to be much higher than that presented in the literature.
The pathophysiology of AF has been intensely studied. Nevertheless, the underlying mechanisms of this complex arrhythmia remain incompletely eluc....
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Protocol
Procedures involving animal subjects were approved by the Ethics Committee of the University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu Mureș, by the Romanian National Sanitary Veterinary and Food Safety Authority and complied with the International Council for Laboratory Animal Science guidelines (Directive 2010/63/EU).
1. Transesophageal atrial burst pacing protocol
- Randomize adult male Wistar rats (200-400 g of bodyweight) into two groups: STIM and SHAM.
- Anesthetize the animals.
- For induction, use 2.5% isoflurane, 4 L/min, 99.5% O2<....
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Results
In a proof-of-concept study, 22 adult male Wistar rats (200-400 g) were randomly assigned into two groups: STIM (n = 15) and SHAM (n = 7). All animals were housed individually in polycarbonate cages, in a climate-controlled room (21-22 °C), having free access to water and dry food throughout the study. The transesophageal stimulation protocol described above was applied to all animals for 10 days, 5 days per week. All animals underwent the same protocol, except that the rats in the SHAM group did not receive active elect.......
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Discussion
The present paper describes an experimental protocol of long-term transesophageal atrial burst pacing for rapid and efficient induction of AF in rats, suitable for both acute and long-term AF studies. The 10-day stimulation protocol described herein has been successfully used to develop a 'secondary spontaneous AF model' (i.e., a model in which, following a period of AF induction by electrical stimulation, AF develops spontaneously)10. However, the duration of the protocol can vary depending on th.......
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Disclosures
The authors have no conflicts of interest.
Acknowledgements
This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI, project number PN-III-P1-1.1-TE-2019-0370, within PNCDI III.
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Materials
| Name | Company | Catalog Number | Comments |
|---|---|---|---|
| Antisedan (Atipamezole Hydrochloride) 5mg / mL, solution for injection | Orion Corporation | 06043/4004 | for Rats use 1 mg / kg |
| Dormitor (Medetomidine Hydrochloride) 1 mg / mL, solution for injection | Orion Corporation | 06043/4003 | for Rats use 0.5 mg / kg |
| E-Z Anesthesia Single Animal System | E-Z Systems Inc | EZ-SA800 | Allows the manipulation of one animal at a time |
| Isoflurane 99.9%, 100 mL | Rompharm Company | N01AB06 | |
| Ketamine 10%, 25 mL | for Rats use 75 mg / kg | ||
| Microcontroller-based cardiac pacemaker for small animals | Developed in our laboratory (See Reference number 10 in the manuscript) | ||
| Surface ECG recording system | Developed in our laboratory (See Reference number 10 in the manuscript) |
References
- Kornej, J., Börschel, C. S., Benjamin, E. J., Schnabel, R. B. Epidemiology of atrial fibrillation in the 21st century: Novel methods and new insights. Circulation Research. 127 (1), 4-20 (2020).
- Hindricks, G., et al.
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