@article{APS7990,
author = {De-Zai Dai},
title = {Vulnerable substrate and multiple ion channel disorder in a diseased heart will be new targets for antiarrhythmic therapy},
journal = {Acta Pharmacologica Sinica},
volume = {21},
number = {4},
year = {2016},
keywords = {},
abstract = {Life-threatening arrhythmia remains a problem contributing to major death in cardiovascular diseases. Till date the antiarrhythmic drugs (AAD) including the Class I and the pure Class III agents have not been recommended for controlling malignant ventricular arrhythmias in a diseased heart, not because of low efficacy but because of an increase in mortality due to their toxic effects. A vulnerable substrate (VS) possessing some properties such as reduced NE and SOD activity, hypertrophied myocardium, and an increase in QT dispersion, is reported to develop in non-infarcted zone of an infarcted heart. Hypertrophied ventricle and exaggerated cardiac arrhythmia can be produced on chronic medication with levothyroxin and this model shares some properties of VS. There is a significant difference in the pattern of disordered ion channels between the congenital long QT syndrome(LQTS) and the acquired heart disease. The affected ion channel in congenital LQTS is single. A novel mutation causing an early appearance of stop codon was discovered in HERG gene resultant with a single disarranged IKr channel leading to a prolonged QT interval. In contrast it is characterised with multi-channels and non-specific disorder in the hypertrophied myocardium in the acquired heart disease. The disordered ion channel is the consequence of the VS lesion influencing the lipid membrane in a diseased heart. The VS and multiple ion channel disorder are provided as new targets to treat cardiac arrhythmias in a diseased heart.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7990}
}