Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.
OBJECTIVE
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.
Schrickel
Jan Wilko
JW
Department of Medicine-Cardiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. jan.schrickel@ukb.uni-bonn.de
Stöckigt
Florian
F
Krzyzak
Wieslaw
W
Paulin
Denise
D
Li
Zhenlin
Z
Lübkemeier
Indra
I
Fleischmann
Bernd
B
Sasse
Philipp
P
Linhart
Markus
M
Lewalter
Thorsten
T
Nickenig
Georg
G
Lickfett
Lars
L
Schröder
Rolf
R
Clemen
Christoph Stephan
CS
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology; D003893:Desmin / Q000172:deficiency; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005838:Genotype; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
D003893:Desmin
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