Schrickel Jan Wilko, Stöckigt Florian, Krzyzak Wieslaw, Paulin Denise, Li Zhenlin, Lübkemeier Indra, Fleischmann Bernd, Sasse Philipp, Linhart Markus, Lewalter Thorsten, Nickenig Georg, Lickfett Lars, Schröder Rolf, Clemen Christoph Stephan
Department of Medicine-Cardiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany.
J Interv Card Electrophysiol. 2010 Aug;28(2):71-80. doi: 10.1007/s10840-010-9482-8.
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.
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.
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.
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.
人类中的结蛋白突变会导致结蛋白相关心肌病，进而引发心力衰竭、房性和室性心律失常以及心源性猝死。中间丝结蛋白在横纹肌细胞和心室传导系统的浦肯野纤维中强烈表达。本研究的目的是在结蛋白缺陷小鼠模型中表征心脏的电生理特性。
本研究考察了结蛋白缺陷对心脏电生理特征的影响。对29只成年结蛋白缺陷（Des-/-）小鼠和19只野生型（Des+/+）小鼠进行了体内电生理研究。此外，在Langendorff灌注心脏上进行了心外膜激动标测。
心内心电图显示房室（AV）、房希（AH）和希室（HV）间期无显著差异。功能测试显示房室结不应期、窦房结恢复时间和文氏点相同。然而，与野生型情况相比，发现Des-/-小鼠的心房不应期显著缩短（23.6±10.3毫秒对31.8±12.5毫秒；p=0.045），但心室不应期延长（33.0±8.7毫秒对26.7±6.5毫秒；p=0.009）。Des-/-小鼠诱发心房颤动的概率显著更高（Des-/-：38%对Des+/+：27%；p=0.0255），而室性心动过速显著减少（Des-/-：7%对Des+/+：21%；p<0.0001）。心外膜激动标测显示Des-/-小鼠心室传导减慢。
Des-/-小鼠表现出心房不应期缩短但心室不应期延长以及心室传导减慢，同时伴有心房颤动诱导性增强和室性心律失常易感性降低。结蛋白缺陷不会导致人类结蛋白病中出现的电生理变化，这表明功能改变而非结蛋白缺失导致了这些患者的心脏改变。
