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dc.contributor.authorLobo-Gonzalez, Manuel 
dc.contributor.authorGalan-Arriola, Carlos 
dc.contributor.authorRossello, Xavier 
dc.contributor.authorGonzález-Del-Hoyo, Maribel
dc.contributor.authorVilchez, Jean Paul 
dc.contributor.authorHiguero-Verdejo, María I
dc.contributor.authorGarcia-Ruiz, Jose M 
dc.contributor.authorLopez-Martin, Gonzalo J. 
dc.contributor.authorSanchez-Gonzalez, Javier 
dc.contributor.authorOliver, Eduardo 
dc.contributor.authorPizarro, Gonzalo 
dc.contributor.authorFuster, Valentin 
dc.contributor.authorIbanez, Borja
dc.identifier.citationBasic Res Cardiol. 2020; 115(5):55es_ES
dc.description.abstractEarly metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.es_ES
dc.description.sponsorshipThis study received funding from the Ministry of Science and Innovation (“RETOS 2019” Grant no. PID2019-107332RB-I00), from the Instituto de Salud Carlos III (ISCIII; PI16/02110) and the European Regional Development Fund (ERDF) “A way of making Europe” (# AC16/00021), and from the Spanish Society of Cardiology through a 2017 Translational Research grant. BI has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-Consolidator Grant agreement no. 819775). M.L received support from a 2015 Severo Ochoa CNIC intramural grant. X.R. received support from the SEC-CNIC CARDIOJOVEN fellowship program. R.F-J is a recipient of funding from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI19/01704) and has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atracción de Talento (2017-T1/BMD-5185) of Comunidad de Madrid. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.titleMetoprolol blunts the time-dependent progression of infarct size.es_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderSociedad Española de Cardiologíaes_ES
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderEuropean Uniones_ES
dc.contributor.funderCentro Nacional de Investigaciones Cardiovasculares (CNIC)es_ES
dc.contributor.funderFundación ProCNICes_ES
dc.contributor.funderComunidad de Madrides_ES
dc.identifier.journalBasic research in cardiologyes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionaleses_ES

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