LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

Author:

Chang Po-Cheng12,Lin Shien-Fong3,Chu Yen24,Wo Hung-Ta12,Lee Hui-Ling5,Huang Yu-Chang12,Wen Ming-Shien12,Chou Chung-Chuan12ORCID

Affiliation:

1. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan

2. Chang Gung University College of Medicine, Taiwan

3. Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan

4. Division of Thoracic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan

5. Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan

Abstract

Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.

Funder

Ministry of Science and Technology, Taiwan

Publisher

Hindawi Limited

Subject

Pharmacology (medical),Cardiology and Cardiovascular Medicine,Pharmacology,General Medicine

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