title: Vulnerable substrate and multiple ion channel disorder in a diseased heart will be new targets for antiarrhythmic therapy.
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.
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. njpdaidz@jlonline.com
authors.forename: D Z
authors.initials: DZ
authors.lastname: Dai
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001599:Berberine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy; D006801:Humans; D007473:Ion Channels; D008133:Long QT Syndrome / Q000188:drug therapy; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C400084:4-chlorobenzyltetrahydroberberine; D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D001599:Berberine; D013482:Superoxide Dismutase; D009638:Norepinephrine