RESUMO
Early 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.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Metoprolol/administração & dosagem , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Administração Intravenosa , Animais , Técnicas de Imagem Cardíaca , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Imageamento por Ressonância Magnética , Masculino , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Suínos , Fatores de TempoRESUMO
OBJECTIVES: To demonstrate the efficacy of a system for comprehensive care transfer (Multilevel Guided Discharge Plan [MGDP]) for frail older patients diagnosed with acute heart failure (AHF) and to validate the results of MGDP implementation under real clinical conditions. The MGDP seeks to reduce the number of adverse outcomes within 30 days of emergency department (ED) discharge. MATERIAL AND METHODS: We will enroll frail patients over the age of 70 years discharged home from the ED with a main diagnosis of AHF. The MGDP includes the following components: 1) a checklist of clinical recommendations and resource activations, 2) scheduling of an early follow-up visit, 3) transfer of information to the primary care doctor, and 4) written instructions for the patient. Phase 1 of the study will be a matched-pair cluster-randomized controlled trial. Ten EDs will be randomly assigned to the intervention group and 10 to the control group. Each group will enroll 480 patients, and the outcomes will be compared between groups. Phase 2 will be a quasi-experimental study of the intervention in 300 new patients enrolled by the same 20 EDs. The outcomes will be compared to those for each Phase-1 group. The main endpoint at 30 days will be a composite of 2 outcomes: revisits to an ED and/for hospitalization for AHF or cardiovascular death. CONCLUSION: The study will assess the efficacy and feasibility of comprehensive MGDP transfer of care for frail older AHF patients discharged home.
OBJETIVO: Demostrar la eficacia de una intervención integral en la transición de cuidados (Plan de Alta Guiado Multinivel, PAGM) para disminuir eventos adversos a 30 días en ancianos frágiles con insuficiencia cardiaca aguda (ICA) dados de alta desde servicios de urgencias (SU) y validar los resultados de dicha intervención en condiciones reales. METODO: Se seleccionarán pacientes 70 años frágiles con diagnóstico principal de ICA dados del alta a su domicilio desde SU. La intervención consistirá en aplicar un PAGM: 1) lista de verificación sobre recomendaciones clínicas y activación de recursos; 2) programación de visita precoz; 3) transmisión de información a atención primaria; 4) hoja de instrucciones al paciente por escrito. Fase 1: ensayo clínico con asignación al azar por conglomerados emparejado. Se asignará de forma aleatoria 10 SU (N = 480) al grupo de intervención y 10 SU (N = 480) al grupo de control. Se compararán los resultados entre grupo de intervención y control. Fase 2: estudio cuasi-experimental. Se realizará la intervención en los 20 SU (N = 300). Se comparará los resultados entre la fase 1 y 2 del grupo de intervención y entre la fase 1 y 2 del grupo de control. La variable principal de resultado es compuesta (revisita a urgencias u hospitalización por ICA o mortalidad de origen cardiovascular) a los 30 días del alta. CONCLUSIONES: El estudio valorará la eficacia y factibilidad de una intervención integral en la transición de cuidados para reducir resultados adversos a 30 días en ancianos frágiles con ICA dados de alta desde los SU.