RESUMEN
We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.
Asunto(s)
Galectina 3/biosíntesis , Insuficiencia Cardíaca/genética , Hipertrofia Ventricular Izquierda/genética , Cadenas Pesadas de Miosina/biosíntesis , Miosina Tipo II/biosíntesis , Péptido Natriurético Encefálico/biosíntesis , Animales , Modelos Animales de Enfermedad , Ecocardiografía , Galectina 3/genética , Regulación de la Expresión Génica , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/patología , Frecuencia Cardíaca/genética , Humanos , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/patología , Isoproterenol/toxicidad , Ratones , Miocardio/patología , Cadenas Pesadas de Miosina/genética , Miosina Tipo II/genética , Péptido Natriurético Encefálico/genética , Sitios de Carácter Cuantitativo/genética , Remodelación Ventricular/genéticaRESUMEN
A comprehensive preoperative assessment of elderly patients undergoing intracranial surgeries can reduce perioperative morbidity and mortality. Elderly patients often present with a wide array of comorbid medical conditions and extensive medication lists, which may influence the preoperative evaluation, anesthetic plan, and perioperative care. This article provides a basic overview of the preoperative assessment of elderly patients undergoing intracranial surgeries.