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Effects of the inhibition of late sodium current by GS967 on stretch-induced changes in cardiac electrophysiology

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Effects of the inhibition of late sodium current by GS967 on stretch-induced changes in cardiac electrophysiology

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dc.contributor.author Canto Serrano, Irene Del es_ES
dc.contributor.author Santamaría, L. es_ES
dc.contributor.author Genovés, P. es_ES
dc.contributor.author Such-Miquel, Luis es_ES
dc.contributor.author Arias-Mutis, Óscar Julián es_ES
dc.contributor.author Zarzoso Muñoz, Manuel es_ES
dc.contributor.author Soler, C. es_ES
dc.contributor.author Parra-Giraldo, G. es_ES
dc.contributor.author Tormos Ferrando, Álvaro es_ES
dc.contributor.author Alberola, Antonio es_ES
dc.contributor.author Such Belenguer, Luis es_ES
dc.contributor.author Chorro, F.J. es_ES
dc.date.accessioned 2019-09-05T20:04:46Z
dc.date.available 2019-09-05T20:04:46Z
dc.date.issued 2018 es_ES
dc.identifier.issn 0920-3206 es_ES
dc.identifier.uri http://hdl.handle.net/10251/125110
dc.description.abstract [EN] PurposeMechanical stretch increases sodium and calcium entry into myocytes and activates the late sodium current. GS967, a triazolopyridine derivative, is a sodium channel blocker with preferential effects on the late sodium current. The present study evaluates whether GS967 inhibits or modulates the arrhythmogenic electrophysiological effects of myocardial stretch.MethodsAtrial and ventricular refractoriness and ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts (n=28) using epicardial multiple electrodes and high-resolution mapping techniques under control conditions and during the perfusion of GS967 at different concentrations (0.03, 0.1, and 0.3M).ResultsOn comparing ventricular refractoriness, conduction velocity and wavelength obtained before stretch had no significant changes under each GS967 concentration while atrial refractoriness increased under GS967 0.3M. Under GS967, the stretch-induced changes were attenuated, and no significant differences were observed between before and during stretch. GS967 0.3M diminished the normal stretch-induced changes resulting in longer (less shortened) atrial refractoriness (13826ms vs 95 +/- 9ms; p<0.01), ventricular refractoriness (155 +/- 18ms vs 124 +/- 16 ms; p<0.01) and increments in spectral concentration (23 +/- 5% vs 17 +/- 2%; p<0.01), the fifth percentile of ventricular activation intervals (46 +/- 8ms vs 31 +/- 3ms; p<0.05), and wavelength of ventricular fibrillation (2.5 +/- 0.5cm vs 1.7 +/- 0.3cm; p<0.05) during stretch. The stretch-induced increments in dominant frequency during ventricular fibrillation (control=38%, 0.03M=33%, 0.1M=33%, 0.3M=14%; p<0.01) and the stretch-induced increments in arrhythmia complexity index (control=62%, 0.03M=41%, 0.1M=32%, 0.3M=16%; p<0.05) progressively decreased on increasing the GS967 concentration.Conclusions GS967 attenuates stretch-induced changes in cardiac electrophysiology. es_ES
dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competiveness (Carlos III Health Institute)/European Regional Development Fund (FEDER) (Grants FIS PI12/00407, PI15/01408, PIE15/00013, CB16/11/00486) and by the Generalitat Valenciana (Grant PROMETEO FASE II 2014/037). es_ES
dc.language Inglés es_ES
dc.publisher Springer-Verlag es_ES
dc.relation.ispartof Cardiovascular Drugs and Therapy es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Mechanoelectric feedback es_ES
dc.subject Myocardial stretch es_ES
dc.subject Late sodium current es_ES
dc.subject GS967 es_ES
dc.subject Ventricular fibrillation es_ES
dc.subject Activation mapping of arrhythmias es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Effects of the inhibition of late sodium current by GS967 on stretch-induced changes in cardiac electrophysiology es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1007/s10557-018-6822-x es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEOII%2F2014%2F037/ES/ESTUDIO MEDIANTE TÉCNICAS CARTOGRÁFICAS AVANZADAS DE LOS MECANISMOS BÁSICOS IMPLICADOS EN LAS ARRITMIAS MALIGNAS Y EN SU CONTROL/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//CB16%2F11%2F00486/ES/ENFERMEDADES CARDIOVASCULARES/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//PI12%2F00407/ES/Utilidad de la estabilización de la homeostasis del calcio intracelular en el control de los procesos fibrilatorios/
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//PI15%2F01408/ES/Efectos de la inhibición de la desacetilación de las histonas en el remodelado post-infarto del sustrato arritmogénico/
dc.relation.projectID info:eu-repo/grantAgreement/ISCIII//PIE15%2F00013/
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Canto Serrano, ID.; Santamaría, L.; Genovés, P.; Such-Miquel, L.; Arias-Mutis, ÓJ.; Zarzoso Muñoz, M.; Soler, C.... (2018). Effects of the inhibition of late sodium current by GS967 on stretch-induced changes in cardiac electrophysiology. Cardiovascular Drugs and Therapy. 32(5):413-425. https://doi.org/10.1007/s10557-018-6822-x es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1007/s10557-018-6822-x es_ES
dc.description.upvformatpinicio 413 es_ES
dc.description.upvformatpfin 425 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 32 es_ES
dc.description.issue 5 es_ES
dc.identifier.pmid 30173392
dc.relation.pasarela S\368706 es_ES
dc.contributor.funder Instituto de Salud Carlos III es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
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