Optical Mapping Approaches on Muscleblind-Like Compound Knockout Mice for Understanding Mechanistic Insights Into Ventricular Arrhythmias in Myotonic Dystrophy

Chung Chuan Chou, Po Cheng Chang, Yi Chia Wei, Kuang Yung Lee*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

14 引文 斯高帕斯(Scopus)

摘要

Background-—Cardiac arrhythmias are common causes of death in patients with myotonic dystrophy (dystrophia myotonica [DM]). Evidence shows that atrial tachyarrhythmia is an independent risk factor for sudden death; however, the relationship is unclear. Methods and Results-—Control wild-type (Mbnl1+/+; Mbnl2+/+ ) and DM mutant (Mbnl1/; Mbnl2+/ ) mice were generated by crossing double heterozygous knockout (Mbnl1+/; Mbnl2+/ ) mice. In vivo electrophysiological study and optical mapping technique were performed to investigate mechanisms of ventricular tachyarrhythmias. Transmission electron microscopy scanning was performed for myocardium ultrastructural analysis. DM mutant mice were more vulnerable to anesthesia medications and program electrical pacing: 2 of 12 mice had sudden apnea and cardiac arrest during premedication of general anesthesia; 9 of the remaining 10 had atrial tachycardia and/or atrioventricular block, but none of the wild-type mice had spontaneous arrhythmias; and 9 of 10 mice had pacing-induced ventricular tachyarrhythmias, but only 1 of 14 of the wild-type mice. Optical mapping studies revealed prolonged action potential duration, slower conduction velocity, and steeper conduction velocity restitution curves in the DM mutant mice than in the wild-type group. Spatially discordant alternans was more easily inducible in DM mutant than wild-type mice. Transmission electron microscopy showed disarranged myofibrils with enlarged vacuole-occupying mitochondria in the DM mutant group. Conclusions-—This DM mutant mouse model presented with clinical myofibril ultrastructural abnormality and cardiac arrhythmias, including atrial tachyarrhythmias, atrioventricular block, and ventricular tachyarrhythmias. Optical mapping studies revealed prolonged action potential duration and slow conduction velocity in the DM mice, leading to vulnerability of spatially discordant alternans and ventricular arrhythmia induction to pacing.

原文英語
文章編號e005191
期刊Journal of the American Heart Association
6
發行號4
DOIs
出版狀態已出版 - 05 04 2017

文獻附註

Publisher Copyright:
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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