Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts

Autores
Diez, Emiliano Raúl; Prado, Natalia Jorgelina; Carrión, Adriana Miriam; Petrich, Elena R.; Ponce Zumino, Amira Zulma; Miatello, Roberto Miguel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 μM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 μM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 μM, P = 0.1718), 4 of 12 (2 μM, P = 0.0361), and 2 of 10 (5 μM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 μM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.
Fil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Prado, Natalia Jorgelina. Universidad Nacional de Cuyo; Argentina
Fil: Carrión, Adriana Miriam. Universidad Nacional de Cuyo; Argentina
Fil: Petrich, Elena R.. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Miatello, Roberto Miguel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
HYPOTONIC CHALLENGE
ISOLATED RAT HEARTS
OXIDATIVE STRESS
REPERFUSION ARRHYTHMIAS
TAMOXIFEN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/92585
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/92585
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat heartsDiez, Emiliano RaúlPrado, Natalia JorgelinaCarrión, Adriana MiriamPetrich, Elena R.Ponce Zumino, Amira ZulmaMiatello, Roberto MiguelHYPOTONIC CHALLENGEISOLATED RAT HEARTSOXIDATIVE STRESSREPERFUSION ARRHYTHMIASTAMOXIFENhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 μM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 μM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 μM, P = 0.1718), 4 of 12 (2 μM, P = 0.0361), and 2 of 10 (5 μM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 μM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.Fil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Prado, Natalia Jorgelina. Universidad Nacional de Cuyo; ArgentinaFil: Carrión, Adriana Miriam. Universidad Nacional de Cuyo; ArgentinaFil: Petrich, Elena R.. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Miatello, Roberto Miguel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaLippincott Williams2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.rarapplication/zipapplication/pdfhttp://hdl.handle.net/11336/92585Diez, Emiliano Raúl; Prado, Natalia Jorgelina; Carrión, Adriana Miriam; Petrich, Elena R.; Ponce Zumino, Amira Zulma; et al.; Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts; Lippincott Williams; Journal Of Cardiovascular Pharmacology; 62; 2; 8-2013; 184-1910160-2446CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/FJC.0b013e318295b611info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/article/00005344-201308000-00010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:35Zoai:ri.conicet.gov.ar:11336/92585instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:35.302CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
title Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
spellingShingle Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
Diez, Emiliano Raúl
HYPOTONIC CHALLENGE
ISOLATED RAT HEARTS
OXIDATIVE STRESS
REPERFUSION ARRHYTHMIAS
TAMOXIFEN
title_short Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
title_full Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
title_fullStr Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
title_full_unstemmed Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
title_sort Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts
dc.creator.none.fl_str_mv Diez, Emiliano Raúl
Prado, Natalia Jorgelina
Carrión, Adriana Miriam
Petrich, Elena R.
Ponce Zumino, Amira Zulma
Miatello, Roberto Miguel
author Diez, Emiliano Raúl
author_facet Diez, Emiliano Raúl
Prado, Natalia Jorgelina
Carrión, Adriana Miriam
Petrich, Elena R.
Ponce Zumino, Amira Zulma
Miatello, Roberto Miguel
author_role author
author2 Prado, Natalia Jorgelina
Carrión, Adriana Miriam
Petrich, Elena R.
Ponce Zumino, Amira Zulma
Miatello, Roberto Miguel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HYPOTONIC CHALLENGE
ISOLATED RAT HEARTS
OXIDATIVE STRESS
REPERFUSION ARRHYTHMIAS
TAMOXIFEN
topic HYPOTONIC CHALLENGE
ISOLATED RAT HEARTS
OXIDATIVE STRESS
REPERFUSION ARRHYTHMIAS
TAMOXIFEN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 μM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 μM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 μM, P = 0.1718), 4 of 12 (2 μM, P = 0.0361), and 2 of 10 (5 μM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 μM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.
Fil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Prado, Natalia Jorgelina. Universidad Nacional de Cuyo; Argentina
Fil: Carrión, Adriana Miriam. Universidad Nacional de Cuyo; Argentina
Fil: Petrich, Elena R.. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Miatello, Roberto Miguel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 μM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 μM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 μM, P = 0.1718), 4 of 12 (2 μM, P = 0.0361), and 2 of 10 (5 μM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 μM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/92585
Diez, Emiliano Raúl; Prado, Natalia Jorgelina; Carrión, Adriana Miriam; Petrich, Elena R.; Ponce Zumino, Amira Zulma; et al.; Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts; Lippincott Williams; Journal Of Cardiovascular Pharmacology; 62; 2; 8-2013; 184-191
0160-2446
CONICET Digital
CONICET
url http://hdl.handle.net/11336/92585
identifier_str_mv Diez, Emiliano Raúl; Prado, Natalia Jorgelina; Carrión, Adriana Miriam; Petrich, Elena R.; Ponce Zumino, Amira Zulma; et al.; Electrophysiological effects of tamoxifen: mechanism of protection against reperfusion arrhythmias in isolated rat hearts; Lippincott Williams; Journal Of Cardiovascular Pharmacology; 62; 2; 8-2013; 184-191
0160-2446
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/FJC.0b013e318295b611
info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/article/00005344-201308000-00010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.rar
application/zip
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.885934

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