LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model

Po Cheng Chang, Shien-Fong Lin, Yen Chu, Hung Ta Wo, Hui Ling Lee, Yu Chang Huang, Ming Shien Wen, Chung Chuan Chou

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number6032631
JournalCardiovascular Therapeutics
Volume2019
DOIs
StatePublished - Jan 1 2019

Fingerprint

Tachycardia
Heart Failure
Myocardial Infarction
Enalapril
Cardiac Arrhythmias
Therapeutics
Western Blotting
Cardiac Electrophysiology
LCZ 696
Proteins
Group Psychotherapy
Ion Channels
Stroke Volume
General Anesthesia
Ligation
Sprague Dawley Rats
Echocardiography
Coronary Vessels
Down-Regulation
Animal Models

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model. / Chang, Po Cheng; Lin, Shien-Fong; Chu, Yen; Wo, Hung Ta; Lee, Hui Ling; Huang, Yu Chang; Wen, Ming Shien; Chou, Chung Chuan.

In: Cardiovascular Therapeutics, Vol. 2019, 6032631, 01.01.2019.

Research output: Contribution to journalArticle

Chang, Po Cheng ; Lin, Shien-Fong ; Chu, Yen ; Wo, Hung Ta ; Lee, Hui Ling ; Huang, Yu Chang ; Wen, Ming Shien ; Chou, Chung Chuan. / LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model. In: Cardiovascular Therapeutics. 2019 ; Vol. 2019.
@article{fd3d969558ed49138e5790287bae679f,
title = "LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model",
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.",
author = "Chang, {Po Cheng} and Shien-Fong Lin and Yen Chu and Wo, {Hung Ta} and Lee, {Hui Ling} and Huang, {Yu Chang} and Wen, {Ming Shien} and Chou, {Chung Chuan}",
year = "2019",
month = "1",
day = "1",
doi = "10.1155/2019/6032631",
language = "English (US)",
volume = "2019",
journal = "Cardiovascular Therapeutics",
issn = "1755-5914",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model

AU - Chang, Po Cheng

AU - Lin, Shien-Fong

AU - Chu, Yen

AU - Wo, Hung Ta

AU - Lee, Hui Ling

AU - Huang, Yu Chang

AU - Wen, Ming Shien

AU - Chou, Chung Chuan

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85069053958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069053958&partnerID=8YFLogxK

U2 - 10.1155/2019/6032631

DO - 10.1155/2019/6032631

M3 - Article

AN - SCOPUS:85069053958

VL - 2019

JO - Cardiovascular Therapeutics

JF - Cardiovascular Therapeutics

SN - 1755-5914

M1 - 6032631

ER -