Metoprolol blunts the time-dependent progression of infarct size

Autor: Carlos Galán-Arriola, Gonzalo J. López-Martín, José Manuel García-Ruiz, María I Higuero-Verdejo, Jean Paul Vilchez, Javier Sánchez-González, Xavier Rossello, Eduardo Oliver, Maribel González-del-Hoyo, Borja Ibanez, Manuel Lobo-Gonzalez, Valentin Fuster, Gonzalo Pizarro
Přispěvatelé: UAM. Departamento de Medicina, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Sociedad Española de Cardiología, European Research Council, Unión Europea, Centro Nacional de Investigaciones Cardiovasculares Carlos III (España), Fundación ProCNIC, Comunidad de Madrid (España), Instituto de Salud Carlos III - ISCIII, European Regional Development Fund (ERDF/FEDER), European Union, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Comunidad de Madrid
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Swine
Ischemia–reperfusion injury
Medicina
Physiology
medicine.medical_treatment
Drug Evaluation
Preclinical
Ischemia
Ischemia-reperfusion injury
Infarction
Myocardial Reperfusion Injury
Acute myocardial infarction
030204 cardiovascular system & hematology
03 medical and health sciences
0302 clinical medicine
Physiology (medical)
Internal medicine
Animals
Medicine
cardiovascular diseases
Myocardial infarction
Saline
Metoprolol
Ejection fraction
business.industry
Myocardium
Original Contribution
medicine.disease
Adrenergic beta-1 Receptor Antagonists
Magnetic Resonance Imaging
Primary ventricular fibrillation
3. Good health
Cardiac Imaging Techniques
Early reperfusion
030104 developmental biology
Disease Progression
Cardiology
ST Elevation Myocardial Infarction
Administration
Intravenous
Cardiology and Cardiovascular Medicine
business
Perfusion
medicine.drug
Zdroj: Biblos-e Archivo. Repositorio Institucional de la UAM
instname
Repisalud
Instituto de Salud Carlos III (ISCIII)
Basic Research in Cardiology
Biblos-e Archivo: Repositorio Institucional de la UAM
Universidad Autónoma de Madrid
ISSN: 1435-1803
0300-8428
2019-1073
Popis: Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (totaln = 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 approximate to 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.
This 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 Sklodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atraccion de Talento (2017-T1/BMD-5185) of Comunidad de Madrid. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovacion (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).
Databáze: OpenAIRE
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