RESUMO
BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies.
Assuntos
Cardiopatias Congênitas/enzimologia , Ventrículos do Coração/enzimologia , Histona Desacetilases/metabolismo , Hipertrofia Ventricular Direita/enzimologia , Função Ventricular Direita , Remodelação Ventricular , Adaptação Fisiológica , Adolescente , Animais , Animais Recém-Nascidos , Estudos de Casos e Controles , Criança , Feminino , Regulação Enzimológica da Expressão Gênica , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia , Histona Desacetilases/genética , Humanos , Hipertrofia Ventricular Direita/genética , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Lactente , Isoenzimas , Masculino , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Background: Delay in care secondary to socioeconomic status (SES) and demographic factors represents an area for potential improvement. Reducing time to surgery in distal radius fracture (DRF) fixation may improve outcomes while reducing cost. The purpose of this study is to investigate the effect of SES on time to surgery in our study population. Methods: Patients undergoing outpatient DRF surgery within an academic healthcare system during a 4-year period were reviewed. Time to surgery and demographic factors were analyzed. The US Census Bureau was used to determine median household income (MHI) for a patient's ZIP code; patients were stratified into three groups based on MHI. Results: A total of 413 patients met inclusion criteria. SES (14.7 d in the low-SES group, 14.0 d in the mid-SES group, and 11.1 d in the high-SES group, P = 0.00063), insurance (11.7 d for insured versus 16.3 d for Medicaid/uninsured, P < 0.0001), race (non-White group: 15.2 d versus White group: 10.9 d, P < 0.0001), and treatment facility (16.2 d at county hospital versus 10.9 d at university hospital, P < 0.0001) were associated with time to surgery in univariate analysis. Multivariate analysis found that only treatment facility was associated with time to surgery. Conclusions: Non-White, uninsured/Medicaid individuals residing in low-SES areas may be more likely to receive care at a safety-net facility and are at greatest risk for delay in time to surgery. Measures aimed to reduce barriers to care, increase healthcare coverage, and improve patient education should be initiated to mitigate these disparities.