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Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study

Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, lead...

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Autores principales: Coppini, Raffaele, Ferrantini, Cecilia, Pioner, Josè Manuel, Santini, Lorenzo, Wang, Zhinuo J., Palandri, Chiara, Scardigli, Marina, Vitale, Giulia, Sacconi, Leonardo, Stefàno, Pierluigi, Flink, Laura, Riedy, Katherine, Pavone, Francesco Saverio, Cerbai, Elisabetta, Poggesi, Corrado, Mugelli, Alessandro, Bueno-Orovio, Alfonso, Olivotto, Iacopo, Sherrid, Mark V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978554/
https://www.ncbi.nlm.nih.gov/pubmed/31998849
http://dx.doi.org/10.1016/j.jacbts.2019.06.004
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author Coppini, Raffaele
Ferrantini, Cecilia
Pioner, Josè Manuel
Santini, Lorenzo
Wang, Zhinuo J.
Palandri, Chiara
Scardigli, Marina
Vitale, Giulia
Sacconi, Leonardo
Stefàno, Pierluigi
Flink, Laura
Riedy, Katherine
Pavone, Francesco Saverio
Cerbai, Elisabetta
Poggesi, Corrado
Mugelli, Alessandro
Bueno-Orovio, Alfonso
Olivotto, Iacopo
Sherrid, Mark V.
author_facet Coppini, Raffaele
Ferrantini, Cecilia
Pioner, Josè Manuel
Santini, Lorenzo
Wang, Zhinuo J.
Palandri, Chiara
Scardigli, Marina
Vitale, Giulia
Sacconi, Leonardo
Stefàno, Pierluigi
Flink, Laura
Riedy, Katherine
Pavone, Francesco Saverio
Cerbai, Elisabetta
Poggesi, Corrado
Mugelli, Alessandro
Bueno-Orovio, Alfonso
Olivotto, Iacopo
Sherrid, Mark V.
author_sort Coppini, Raffaele
collection PubMed
description Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients.
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spelling pubmed-69785542020-01-29 Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study Coppini, Raffaele Ferrantini, Cecilia Pioner, Josè Manuel Santini, Lorenzo Wang, Zhinuo J. Palandri, Chiara Scardigli, Marina Vitale, Giulia Sacconi, Leonardo Stefàno, Pierluigi Flink, Laura Riedy, Katherine Pavone, Francesco Saverio Cerbai, Elisabetta Poggesi, Corrado Mugelli, Alessandro Bueno-Orovio, Alfonso Olivotto, Iacopo Sherrid, Mark V. JACC Basic Transl Sci PRECLINICAL RESEARCH Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients. Elsevier 2019-10-09 /pmc/articles/PMC6978554/ /pubmed/31998849 http://dx.doi.org/10.1016/j.jacbts.2019.06.004 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle PRECLINICAL RESEARCH
Coppini, Raffaele
Ferrantini, Cecilia
Pioner, Josè Manuel
Santini, Lorenzo
Wang, Zhinuo J.
Palandri, Chiara
Scardigli, Marina
Vitale, Giulia
Sacconi, Leonardo
Stefàno, Pierluigi
Flink, Laura
Riedy, Katherine
Pavone, Francesco Saverio
Cerbai, Elisabetta
Poggesi, Corrado
Mugelli, Alessandro
Bueno-Orovio, Alfonso
Olivotto, Iacopo
Sherrid, Mark V.
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title_full Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title_fullStr Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title_full_unstemmed Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title_short Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study
title_sort electrophysiological and contractile effects of disopyramide in patients with obstructive hypertrophic cardiomyopathy: a translational study
topic PRECLINICAL RESEARCH
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978554/
https://www.ncbi.nlm.nih.gov/pubmed/31998849
http://dx.doi.org/10.1016/j.jacbts.2019.06.004
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