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dc.contributor.authorDel Canto, Irene
dc.contributor.authorSuch-Miquel, Luis
dc.contributor.authorBrines, Laia
dc.contributor.authorSoler, Carlos
dc.contributor.authorZarzoso, Manuel
dc.contributor.authorCalvo, Conrado
dc.contributor.authorParra, Germán
dc.contributor.authorTormos, Álvaro
dc.contributor.authorAlberola, Antonio
dc.contributor.authorMillet, José
dc.contributor.authorSuch, Luis
dc.contributor.authorChorro, Francisco J.
dc.date.accessioned2017-07-10T07:59:45Z
dc.date.available2017-07-10T07:59:45Z
dc.date.issued2016
dc.identifier.citationCANTO, Irene, et al. Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback. Clinical and Experimental Pharmacology and Physiology, 2016, vol. 43, no 11, p. 1062-1070.ca_CA
dc.identifier.issn0305-1870
dc.identifier.issn1440-1681
dc.identifier.urihttp://hdl.handle.net/10234/168221
dc.description.abstractJTV-519 is a 1,4-benzothiazepine derivative with multichannel effects that inhibits Ca2+ release from the sarcoplasmic reticulum and stabilizes the closed state of the ryanodine receptor, preventing myocardial damage and the induction of arrhythmias during Ca2+ overload. Mechanical stretch increases cellular Na+ inflow, activates the reverse mode of the Na+/Ca2+ exchanger, and modifies Ca2+ handling and myocardial electrophysiology, favoring arrhythmogenesis. This study aims to determine whether JTV-519 modifies the stretch-induced manifestations of mechanoelectric feedback. The ventricular fibrillation (VF) modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n=9) or during JTV-519 perfusion: 0.1 μmol/L (n=9) and 1 μmol/L (n=9). Spectral and mapping techniques were used to establish the baseline, stretch and post-stretch VF characteristics. JTV-519 slowed baseline VF and decreased activation complexity. These effects were dose-dependent (baseline VF dominant frequency: control=13.9±2.2 Hz; JTV 0.1 μmol/L=11.1±1.1 Hz, P<.01; JTV 1 μmol/L=6.6±1.1 Hz, P<.0001). The stretch-induced acceleration of VF (control=38.8%) was significantly reduced by JTV-519 0.1 μmol/L (19.8%) and abolished by JTV 1 μmol/L (−1.5%). During stretch, the VF activation complexity index was reduced in both JTV-519 series (control=1.60±0.15; JTV 0.1 μmol/L=1.13±0.3, P<.0001; JTV 1 μmol/L=0.57±0.21, P<.0001), and was independently related to VF dominant frequency (R=.82; P<.0001). The fifth percentile of the VF activation intervals, conduction velocity and wavelength entered the multiple linear regression model using dominant frequency as the dependent variable (R=−.84; P<.0001). In conclusion, JTV-519 slowed and simplified the baseline VF activation patterns and abolished the stretch-induced manifestations of mechanoelectric feedback.ca_CA
dc.description.sponsorShipThis work was supported by the Spanish Ministry of Economy and Competitiveness (Carlos III Health Institute)/European FEDER Grants FIS PI12/00407, PI15/01408, PIE15/00013 and RETIC “RIC” RD12/0042/0048, and by Generalitat Valenciana Grant PROMETEO FASEII 2014/037.ca_CA
dc.format.extent9 p.ca_CA
dc.language.isoengca_CA
dc.publisherWileyca_CA
dc.relation.isPartOfClinical and Experimental Pharmacology and Physiology, 2016, vol. 43, no 11ca_CA
dc.rightsCopyright © John Wiley & Sons, Inc. All Rights Reservedca_CA
dc.subjectJTV-519ca_CA
dc.subjectK201ca_CA
dc.subjectmappingca_CA
dc.subjectmechanoelectric feedbackca_CA
dc.subjectmyocardial stretchca_CA
dc.subjectventricular fibrillationca_CA
dc.titleEffects of JTV-519 on stretch-induced manifestations of mechanoelectric feedbackca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1111/1440-1681.12630
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_CA
dc.relation.publisherVersionhttp://onlinelibrary.wiley.com/doi/10.1111/1440-1681.12630/fullca_CA


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