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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inotropic and Antiarrhythmic Transmural Actions of Ranolazine in a Cellular Model of Type 3 Long QT Syndrome

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Author(s):
Victor Martins Miranda [1] ; Samuel Santos Beserra [2] ; Danilo Roman-Campos [3]
Total Authors: 3
Affiliation:
[1] Universidade Federal de São Paulo. Departamento de Biofísica - Brasil
[2] Universidade Federal de São Paulo. Departamento de Biofísica - Brasil
[3] Universidade Federal de São Paulo. Departamento de Biofísica - Brasil
Total Affiliations: 3
Document type: Journal article
Source: Arquivos Brasileiros de Cardiologia; v. 114, n. 4, p. 732-735, 2020-05-29.
Abstract

Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells. (AU)

FAPESP's process: 14/09861-1 - The role of late sodium current in the inherited and acquired cardiac arrhythmias: from the biophysics properties to new therapeutic targets
Grantee:Danilo Roman Campos
Support Opportunities: Research Grants - Young Investigators Grants