dc.contributor.author | Ramirez, Rafael J | |
dc.contributor.author | Takemoto, Yoshio | |
dc.contributor.author | Martins, Raphaël P | |
dc.contributor.author | Filgueiras-Rama, David | |
dc.contributor.author | Ennis, Steven R | |
dc.contributor.author | Mironov, Sergey | |
dc.contributor.author | Bhushal, Sandesh | |
dc.contributor.author | Deo, Makarand | |
dc.contributor.author | Rajamani, Sridharan | |
dc.contributor.author | Berenfeld, Omer | |
dc.contributor.author | Belardinelli, Luiz | |
dc.contributor.author | Jalife, Jose | |
dc.contributor.author | Pandit, Sandeep V | |
dc.date.accessioned | 2020-05-06T09:01:18Z | |
dc.date.available | 2020-05-06T09:01:18Z | |
dc.date.issued | 2019-10 | |
dc.identifier.citation | Circ Arrhythm Electrophysiol. 2019; 12(10):e005557 | es_ES |
dc.identifier.issn | 1941-3149 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9925 | |
dc.description.abstract | BACKGROUND: Ranolazine inhibits Na+ current (INa), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF). METHODS: PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped. RESULTS: In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (P<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm-2 s-1 (P<0.001) in left atrial epicardium (LAepi), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz; P<0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm-2 s-1; P=ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing INa decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions. CONCLUSIONS: PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF. | es_ES |
dc.description.sponsorship | This work was supported by: grants from the National Institutes of Health National Heart, Lung, and Blood Institute R01-HL118304 (Dr Berenfeld) and R01-HL122352 (Dr Jalife); the Leducq Foundation (Drs Jalife, Berenfeld, and Pandit); the University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research (Dr Jalife); Ministerio de Economia y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER; Dr Jalife); the JHRS fellowship program from Medtronic Japan, Uehara Memorial Foundation (Dr Takemoto); American Heart Association postdoctoral fellowship (Dr Takemoto); research grants from Gilead Sciences Inc (Drs Jalife and Pandit); and research support and assistance with implantable devices from St Jude Medical and Medtronic Inc (Drs Jalife and Berenfeld). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Heart Association (AHA) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Antiarrhythmic drugs | es_ES |
dc.subject | Atrial fibrillation | es_ES |
dc.subject | Catheter ablation | es_ES |
dc.subject | Dofetilide | es_ES |
dc.subject | Dominant frequency | es_ES |
dc.subject | Ranolazine | es_ES |
dc.subject | Rotors | es_ES |
dc.title | Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 31594392 | es_ES |
dc.format.volume | 12 | es_ES |
dc.format.number | 10 | es_ES |
dc.format.page | e005557 | es_ES |
dc.identifier.doi | 10.1161/CIRCEP.117.005557 | es_ES |
dc.contributor.funder | NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) | |
dc.contributor.funder | Fondation Leducq | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | American Heart Association | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1941-3084 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1161/CIRCEP.117.005557 | es_ES |
dc.identifier.journal | Circulation. Arrhythmia and electrophysiology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Arritmias Cardíacas | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Desarrollo Avanzado sobre Mecanismos y Terapias de las Arritmias | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |