Cardiac Conduction Disturbances and Differential Effects on Atrial and Ventricular Electrophysiological Properties in Desmin Deficient Mice

Overview

Journal J Interv Card Electrophysiol

Publisher Springer

Date 2010 Apr 15

PMID 20390331

Citations 19

Authors

Jan Wilko Schrickel

Florian Stockigt

Wieslaw Krzyzak

Denise Paulin

Zhenlin Li

Indra Lubkemeier

Bernd Fleischmann

Philipp Sasse

Markus Linhart

Thorsten Lewalter

Georg Nickenig

Lars Lickfett

Rolf Schroder

Christoph Stephan Clemen

Affiliations

Soon will be listed here.

Abstract

Purpose: Desmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is strongly expressed in striated muscle cells and in Purkinje fibers of the ventricular conduction system. The aim of the present study was to characterize electrophysiological cardiac properties in a desmin-deficient mouse model.

Methods: The impact of desmin deficiency on cardiac electrophysiological characteristics was examined in the present study. In vivo electrophysiological studies were carried out in 29 adult desmin deficient (Des-/-) and 19 wild-type (Des+/+) mice. Additionally, epicardial activation mapping was performed in Langendorff-perfused hearts.

Results: Intracardiac electrograms showed no significant differences in AV, AH, and HV intervals. Functional testing revealed equal AV-nodal refractory periods, sinus-node recovery times, and Wenckebach points. However, compared to the wild-type situation, Des-/- mice were found to have a significantly reduced atrial (23.6+/-10.3 ms vs. 31.8+/-12.5 ms; p=0.045), but prolonged ventricular refractory period (33.0+/-8.7 ms vs. 26.7+/-6.5 ms; p=0.009). The probability of induction of atrial fibrillation was significantly higher in Des-/- mice (Des-/-: 38% vs. Des+/+: 27%; p=0.0255), while ventricular tachycardias significantly were reduced (Des-/-: 7% vs. Des+/+: 21%; p<0.0001). Epicardial activation mapping showed slowing of conduction in the ventricles of Des-/- mice.

Conclusions: Des-/- mice exhibit reduced atrial but prolonged ventricular refractory periods and ventricular conduction slowing, accompanied by enhanced inducibility of atrial fibrillation and diminished susceptibility to ventricular arrhythmias. Desmin deficiency does not result in electrophysiological changes present in human desminopathies, suggesting that functional alterations rather than loss of desmin cause the cardiac alterations in these patients.

Citing Articles

Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.

Owais A, Barney M, Ly O, Brown G, Chen H, Sridhar A JACC Basic Transl Sci. 2024; 9(7):918-934.

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Unraveling Impacts of Chamber-Specific Differences in Intercalated Disc Ultrastructure and Molecular Organization on Cardiac Conduction.

Struckman H, Moise N, King D, Soltisz A, Buxton A, Dunlap I JACC Clin Electrophysiol. 2023; 9(12):2425-2443.

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Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice.

Murphy M, Kannankeril P, Murray K Front Physiol. 2023; 14:1149023.

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Desmin variants: Trigger for cardiac arrhythmias?.

Su W, van Wijk S, Brundel B Front Cell Dev Biol. 2022; 10:986718.

PMID: 36158202 PMC: 9500482. DOI: 10.3389/fcell.2022.986718.

PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation.

Ezeani M, Prabhu S Mol Cell Biochem. 2022; 478(3):471-490.

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