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dc.contributor.authorLee, Peter
dc.contributor.authorQuintanilla, Jorge G. 
dc.contributor.authorAlfonso-Almazan, Jose M. 
dc.contributor.authorGalan-Arriola, Carlos 
dc.contributor.authorYan, Ping
dc.contributor.authorSanchez-Gonzalez, Javier 
dc.contributor.authorPérez-Castellano, Nicasio
dc.contributor.authorPérez-Villacastín, Julián
dc.contributor.authorIbanez, Borja 
dc.contributor.authorLoew, Leslie M
dc.contributor.authorFilgueiras-Rama, David
dc.identifier.citationCardiovasc Res. 2019; 115(11):1659-71es_ES
dc.description.abstractAIMS: Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. METHODS AND RESULTS: First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63-138) cm/s vs. 51 (41-64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217-254) ms vs. 192 (182-233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min-1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. CONCLUSIONS: In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.es_ES
dc.description.sponsorshipThe CNIC is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC is a Severo Ochoa Center of Excellence (SEV-2015-0505). This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458), the Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission (ERA-CVD Joint Call [JTC2016/APCIN-ISCIII-2016], grant#AC16/00021). The study was also partially supported by the Fundacio´n Interhospitalaria para la Investigacio´n Cardiovascular (FIC) and the Heart Rhythm section of the Spanish Society of Cardiology. The work at the University of Connecticut was supported by grant EB001963 from the National Institutes of Health.es_ES
dc.publisherOxford University Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectIn vivo imaginges_ES
dc.subjectCardiac fibrillationes_ES
dc.subjectOptical mappinges_ES
dc.subjectVoltage-sensitive dyeses_ES
dc.titleIn vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig modelses_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderFundación ProCNIC
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderEuropean Commission
dc.contributor.funderFundación Interhospitalaria de Investigación Cardiovascular
dc.contributor.funderSociedad Española de Cardiología
dc.contributor.funderNational Institutes of Health (United States)
dc.identifier.journalCardiovascular researches_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Desarrollo Avanzado sobre Mecanismos y Terapias de las Arritmiases_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES

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Atribución-NoComercial 4.0 Internacional
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