Electrophysiologic effects of sacubitril in different arrhythmia models

Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. Aim of this study was to assess the impact of acute sacubitril treatment in different arrhythmia models. Sacubitril was administered (3, 5, 10 μM) in 12 isolated rabbit hearts. Further 12 hearts were tre...

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Bibliographic Details
Published in:European journal of pharmacology 2022-02, Vol.917, p.174747, Article 174747
Main Authors: Ellermann, Christian, Dimanski, Darian, Wolfes, Julian, Rath, Benjamin, Leitz, Patrick, Willy, Kevin, Wegner, Felix K., Eckardt, Lars, Frommeyer, Gerrit
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Aminobutyrates - pharmacology
Animals
Anti-Arrhythmia Agents - pharmacology
Anti-Arrhythmia Agents - therapeutic use
Arrhythmia
Arrhythmias, Cardiac - drug therapy
Arrhythmias, Cardiac - physiopathology
Biphenyl Compounds - pharmacology
Disease Models, Animal
Drug Combinations
Electrophysiological Phenomena - drug effects
Heart failure
Long QT syndrome
Male
Neprilysin - antagonists & inhibitors
Rabbits
Sacubitril
Tetrazoles - pharmacology
Valsartan - pharmacology
Valsartan - therapeutic use
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Summary:Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. Aim of this study was to assess the impact of acute sacubitril treatment in different arrhythmia models. Sacubitril was administered (3, 5, 10 μM) in 12 isolated rabbit hearts. Further 12 hearts were treated with erythromycin to simulate long-QT-syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long-QT-syndrome-3 (LQT3). Both LQT-groups were treated with sacubitril (5 μM) additionally. Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol and sacubitril (5 μM) was added afterwards. With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarisation (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD (- 21 ms, p 
ISSN:0014-2999
1879-0712
1879-0712
DOI:10.1016/j.ejphar.2022.174747