標題: Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction Model
作者: Chang, Po-Cheng
Wo, Hung-Ta
Lee, Hui-Ling
Lin, Shien-Fong
Chu, Yen
Wen, Ming-Shien
Chou, Chung-Chuan
分子醫學與生物工程研究所
Institute of Molecular Medicine and Bioengineering
關鍵字: Heart failure;ventricular arrhythmia;sacubitril/valsartan (LCZ696)
公開日期: 1-六月-2020
摘要: Background: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. Methods and Results: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. Conclusions: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.
URI: http://dx.doi.org/10.1016/j.cardfail.2020.03.007
http://hdl.handle.net/11536/154979
ISSN: 1071-9164
DOI: 10.1016/j.cardfail.2020.03.007
期刊: JOURNAL OF CARDIAC FAILURE
Volume: 26
Issue: 6
起始頁: 527
結束頁: 537
顯示於類別:期刊論文