Dataset Information

Muscarinic acetylcholine receptors M₂ are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

ABSTRACT:

Background

Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone.

Aim

To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M₂) and the G protein-gated inwardly rectifying K⁺ (GIRK4) channel that mediates the cardiac I_K,ACh current.

Method

Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M₂ receptor and the GIRK4 subunit of the I_KACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9).

Results

The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M₂ receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M₂ and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles.

Conclusion

Here, we demonstrate the involvement of the m₂R-I_K,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M₂ receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

SUBMITTER: Nissen SD

PROVIDER: S-EPMC10687567 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Muscarinic acetylcholine receptors M<sub>2</sub> are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Nissen Sarah Dalgas SD Saljic Arnela A Carstensen Helena H Braunstein Thomas Hartig TH Hesselkilde Eva Melis EM Kjeldsen Sofie Troest ST Hopster-Iversen Charlotte C D'Souza Alicia A Jespersen Thomas T Buhl Rikke R

Frontiers in cardiovascular medicine 20231116

<h4>Background</h4>Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone.<h4>Aim</h4>To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M<sub>2</sub>) and the G protein-gated inwardly rectifying K<sup>+</sup> (GIRK4) channel that mediates the cardiac ...[more]

PMID: 38034369

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Project description:BackgroundEbstein's anomaly occurs when there is an apical displacement of the tricuspid valve with septal and posterior valve leaflets tethering. This condition often occurs in association with other congenital, structural, or conduction system diseases, including intracardiac shunts, valvular lesions, arrhythmias, accessory conduction pathways, and first-degree atrioventricular (AV) block. We present for the first time a case of a patient with Ebstein's anomaly who presented with second-degree Mobitz II AV block and was successfully treated with conduction system pacing (CSP) due to her young age and the likelihood of a long-term high percentage of pacing.Case summaryWe present a case of a 42-year-old lady with a background of complex congenital heart disease, including severe pulmonary stenosis, Ebstein anomaly, and atrial septal defect (ASD). She required complex surgical intervention, including tricuspid valve (TV) repair and subsequently replacement, ASD closure, and pulmonary balloon valvuloplasty. She presented to our hospital with symptomatic second-degree Mobitz II AV block (dizziness, shortness of breath, and exercise intolerance) and right bundle branch block (RBBB) on her baseline ECG. Her echocardiogram showed dilated right ventricle (RV) and left ventricle (LV) with low normal LV systolic function. Due to her young age and the likelihood of a long-term high percentage of RV pacing, we opted for CSP after a detailed discussion and patient consent. The distal HIS position is the preferred pacing strategy at our centre. We could not cross the TV with the standard Medtronic C315 HIS catheter, so we had to use the deflectable C304 HIS catheter. Mapping and pacing of the distal HIS bundle were achieved by Medtronic Selectsecure 3830, 69 cm lead. HIS bundle pacing led to the correction of both second-degree Mobitz II AV block and pre-existing RBBB. The implantation was uneventful, and the patient was discharged home the next day without any acute complications.DiscussionDistal HIS pacing is feasible in patients with surgically treated complex Ebstein anomaly and heart block. This approach can normalize the QRS complex with a high probability of preserving or improving LV function.

Dataset Information

Muscarinic acetylcholine receptors M₂ are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Background

Aim

Method

Results

Conclusion

Publications

Muscarinic acetylcholine receptors M<sub>2</sub> are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Background

Aim

Method

Results

Conclusion

Publications

Muscarinic acetylcholine receptors M&lt;sub&gt;2&lt;/sub&gt; are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Muscarinic acetylcholine receptors M₂ are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Muscarinic acetylcholine receptors M<sub>2</sub> are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.