RESUMO
Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.
Assuntos
Cardiopatias Congênitas/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Sistema Linfático/fisiopatologia , Vasos Linfáticos/fisiopatologia , Circulação Pulmonar/fisiologia , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Animais , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Hemodinâmica/fisiologia , Pulmão/metabolismo , Sistema Linfático/metabolismo , Vasos Linfáticos/metabolismo , Óxido Nítrico/metabolismo , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar/genética , Fluxo Sanguíneo Regional/genética , Fluxo Sanguíneo Regional/fisiologia , Ovinos , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: To determine B-type natriuretic peptide (BNP) levels in infants and children with acute lung injury (ALI), and to investigate associations between BNP levels and clinical outcome. DESIGN: Prospective observational study. SUBJECTS: After informed consent, plasma was collected from 48 pediatric patients on day 1 of ALI. METHODOLOGY: Plasma BNP levels were measured by immunoassay on day 1 of ALI in 48 pediatric patients. Associations between BNP levels and outcome were determined. RESULTS: The mean PaO(2)/FiO(2) at the onset of ALI was 155 (+/-74) and BNP values ranged from 5 to 2,060 pg/ml with a mean of 109 (+/-311). BNP levels were inversely correlated with ventilator-free days (Spearman rho -0.30, P = 0.04), and positively correlated with exhaled tidal volume (Spearman rho 0.44, P = 0.02). BNP levels were higher in patients receiving inotropic support (n = 12) than patients not receiving inotropic support (n = 33, P = 0.02). BNP levels were correlated with PRISM III scores (Spearman rho 0.55, P < 0.001) and PELOD scores (Spearman rho 0.4, P = 0.006). Mortality for the cohort was 15%. BNP levels were higher in non-survivors (n = 7) than survivors (n = 41, P = 0.055). CONCLUSIONS: BNP levels are elevated in children with ALI/ARDS early in the disease course, and increased levels are associated with worse clinical outcome.
