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Updated: Dec 25, 2025
Transthoracic Echocardiographic Examination in the Rabbit Model
Published on: June 1, 2019
Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction
Po-Cheng Chang1, Hung-Ta Wo2, Hui-Ling Lee3
1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou; Chang Gung University College of Medicine, Taoyuan.
Insights
Sacubitril/valsartan (LCZ696) therapy improved heart function and reduced arrhythmias in a myocardial infarction (MI) heart failure (HF) rabbit model. LCZ696 therapy altered electrophysiologic remodeling and CaMKII-p expression, decreasing ventricular tachyarrhythmia inducibility.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Coronary artery disease is a leading cause of heart failure (HF).
- Understanding mechanisms of arrhythmia reduction in HF is crucial.
- Myocardial infarction (MI) often leads to HF and arrhythmias.
Purpose of the Study:
- To investigate the anti-arrhythmic mechanisms of sacubitril/valsartan (LCZ696) in a rabbit model of MI-induced HF.
- To elucidate how LCZ696 therapy affects electrophysiologic remodeling and ventricular tachyarrhythmia inducibility.
Main Methods:
- A rabbit model with chronic MI and HF was established.
- Animals were treated with placebo, valsartan, or sacubitril/valsartan (LCZ696).
- Electrophysiologic studies and optical mapping were performed; key parameters and CaMKII-p expression were analyzed.
Main Results:
- LCZ696 significantly improved left ventricular ejection fraction and reduced ventricular tachyarrhythmia inducibility compared to placebo and valsartan.
- LCZ696 therapy shortened action potential duration, reduced intracellular calcium tau, increased conduction velocity, and decreased alternans inducibility.
- Sacubitril/valsartan reduced phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression.
Conclusions:
- Sacubitril/valsartan (LCZ696) effectively ameliorated cardiac function impairment and electrophysiologic remodeling in a chronic MI-HF rabbit model.
- LCZ696 therapy reduced ventricular tachyarrhythmia inducibility, potentially through altered CaMKII-p expression.
- LCZ696 demonstrates significant potential in managing arrhythmias associated with heart failure post-myocardial infarction.
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.
