Name: transesophageal atrial burst pacing for atrial fibrillation induction in rats
Uploaded: 2022-02-14T15:00:00
Description: Watch this Scientific Journal Video about Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats at JoVE.com

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.

Procedures involving animal subjects were approved by the Ethics Committee of the University of Medicine, Pharmacy, Science and Technology &#34;George Emil Palade&#34; of T&#226;rgu Mure&#537;, 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
<ol>
	<li>Randomize adult male Wistar rats (200-400 g of ...

<ol>
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From epidemiology and pathophysiology to therapeutic implications.</a> Canadian Journal of Cardiology. 34 (11), 1492-1502 (2018).</li><li>Nishida, K., Michael, G., Dobrev, D., Nattel, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+atrial+fibrillation:+clinical+insights+and+scientific+opportunities.">Animal models for atrial fibrillation: clinical insights and scientific opportunities.</a> Europace. 12 (2), 160-172 (2010).</li><li>Qiu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=DL-3-n-Butylphthalide+reduces+atrial+fibrillation+susceptibility+by+inhibiting+atrial+structural+remodeling+in+rats+with+heart+failure.">DL-3-n-Butylphthalide reduces atrial fibrillation susceptibility by inhibiting atrial structural remodeling in rats with heart failure.</a> Naunyn-Schmiedeberg's Archives of Pharmacology. 391 (3), 323-334 (2018).</li></ol>

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...

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 elucidated and this reflects in the limited therapeutic options, with questionable efficacy. Animal studies have brought important insights into our understanding regarding AF pathophysiology and therapeutic management. Reentry, one of the main mechanisms involved in AF pathogenesis3, requires a certain mass of myocardial tissue in order to occur. Thus, large animals have generally been preferred in AF studies, whereas, due to the small size of their atria, rodents have long been considered &#39;resistant&#39; to AF. However, the use of large animals is hampered mostly by handling difficulties. Meanwhile, although spontaneous AF has been shown to occur in rats4, long-term follow-up (up to 50 weeks) is required for the arrhythmia to occur in those models5. Models that ensure rapid AF occurrence in small rodents have also been developed. Most often, those models use acute electrical stimulation, often in the presence of other favoring conditions, such as concomitant parasympathetic stimulation or asphyxia, to artificially induce AF6,7. Although efficient, such models do not allow the evaluation of critical AF-related features, such as the progressive electrical, structural, autonomic, or molecular remodeling of the atria, nor the effects of conventional or non-conventional antiarrhythmic drugs on the atrial substrate or on the risk of ventricular pro-arrhythmia8,9.
The present work describes an experimental protocol of long-term transesophageal atrial burst pacing for rapid and efficient induction of AF in rats. The protocol is suitable for both acute and long-term studies and 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.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Antisedan (Atipamezole Hydrochloride) 5mg / mL, solution for injection</td>
			<td>Orion Corporation</td>
			<td>06043/4004</td>
			<td>for Rats use 1 mg / kg</td>
		</tr>
		<tr>
			<td>Dormitor (Medetomidine Hydrochloride) 1 mg / mL, solution for injection</td>
			<td>Orion Corporation</td>
			<td>06043/4003</td>
			<td>for Rats use 0.5 mg / kg</td>
		</tr>
		<tr>
			<td>E-Z Anesthesia Single Animal System</td>
			<td>E-Z Systems Inc</td>
			<td>EZ-SA800</td>
			<td>Allows the manipulation of one animal at a time</td>
		</tr>
		<tr>
			<td>Isoflurane 99.9%, 100 mL</td>
			<td>Rompharm Company</td>
			<td>N01AB06</td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine 10%, 25 mL</td>
			<td></td>
			<td></td>
			<td>for Rats use 75 mg / kg</td>
		</tr>
		<tr>
			<td>Microcontroller-based cardiac pacemaker for small animals</td>
			<td></td>
			<td></td>
			<td>Developed in our laboratory (See Reference number 10 in the manuscript)</td>
		</tr>
		<tr>
			<td>Surface ECG recording system</td>
			<td></td>
			<td></td>
			<td>Developed in our laboratory (See Reference number 10 in the manuscript)</td>
		</tr>
	</tbody>
</table>

transesophageal atrial burst pacing for atrial fibrillation induction in rats

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.

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 &#176;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 ...

Watch this Scientific Journal Video about Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats at JoVE.com

Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats

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.

Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. ...

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