Transesophageal Electrophysiological Testing in Mouse Atrial Fibrillation Research

Atrial fibrillation (AF) is one of the most common clinical arrhythmias and poses a serious threat to patients' health. With well-established gene-editing methods and relatively short disease-modeling timelines, mice are widely used to study AF mechanisms. Yet mice rarely develop AF spontaneously. Researchers therefore use electrical stimulation to induce AF and assess how genes or drugs affect AF susceptibility. Transesophageal electrophysiology offers several practical advantages: it does not require opening the chest, is less invasive, and is relatively straightforward to perform. Drawing on a published study from a team at the First Affiliated Hospital of Zhengzhou University, this article reviews a mouse transesophageal electrophysiology protocol and the key points for in vivo phenotyping.

Figure 1. Key X Sciences equipment for mouse transesophageal electrophysiology testing.

1. In vivo assessment: transesophageal electrophysiology for AF susceptibility

The study used two genetically modified mouse models:

• Usp10-CTg: cardiomyocyte-specific Usp10 overexpression.

• Usp10-CKO: cardiomyocyte-specific Usp10 knockout.

The investigators used a Key X Sciences mouse esophageal electrophysiology catheter and a dual-channel programmable electrical stimulator. Decremental-cycle-length burst pacing was used to assess the ability to induce AF.

2. Standardized stimulation protocol

1. Use sex-matched mice, anesthetize them with 1% sodium pentobarbital, and maintain body temperature with a heating pad.

2. Place the mouse esophageal electrophysiology catheter in the esophagus near the posterior wall of the left atrium.

3. Program five decremental pacing cycle lengths: 50, 40, 30, 25, and 20 ms. Deliver a 15-second stimulus train at each cycle length, with 3 minutes between trains.

4. Define an AF episode as a rapid, irregular atrial rhythm with irregularly irregular R-R intervals lasting at least 1 second.

5. Evaluate AF incidence and mean AF duration. Analyze the data blinded to experimental group to reduce observer bias.

3. Key in vivo phenotype findings

• Angiotensin II (Ang II) treatment in wild-type mice: left atrial enlargement and atrial fibrosis increased, while AF incidence rose and episodes lasted longer.

• USP10 overexpression: left atrial enlargement and atrial fibrosis were significantly attenuated, while AF incidence and episode duration decreased.

• Cardiomyocyte-specific USP10 knockout: Ang II-associated atrial structural damage and AF susceptibility were further exacerbated.

These in vivo electrophysiological findings provide evidence that USP10 attenuates Ang II-induced atrial remodeling and reduces AF susceptibility in this mouse model.

4. Methodological considerations

High stimulation intensity or rapid pacing may activate vagal nerves near the esophagus and cause atrioventricular block, complicating AF classification. Pilot experiments should be used to optimize stimulation parameters. If needed, atropine may be used to block vagal effects, or animals showing atrioventricular block may be excluded from the analysis.

5. Summary

Transesophageal electrophysiology can assess AF susceptibility in mice without opening the chest, making it useful for studies of genetic or drug interventions. A standardized stimulation protocol, explicit AF criteria, and blinded analysis are central to obtaining reliable in vivo electrophysiological results.

Reference

Fu W, et al. USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1. JCI Insight. 2026;11(16):e195761. https://doi.org/10.1172/jci.insight.195761