RESUMO
OBJECTIVE: To examine the role of endogenous nitric oxide (NO) and endothelin-1 (ET-1) in the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) and to determine whether inhaled NO, currently under investigation as a new therapy for PPHN, affects plasma concentrations of these vasoactive mediators. METHODS: Circulating ET-1 and cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay in 15 healthy term newborn infants and 46 newborn infants with PPHN enrolled in a randomized, controlled trial of inhaled NO. These concentrations were followed up longitudinally and compared between the NO and the conventionally treated group. RESULTS: Concentrations of ET-1 were significantly higher and cGMP concentrations significantly lower in infants with PPHN compared with healthy newborn infants (median ET-1, 28 vs 11 pmol/L; p = 0.0001; median cGMP, 35 vs 61 pmol/ml; p = 0.0001, respectively). ET-1 concentrations showed an upward trend at 1 and 24 hours of treatment and a subsequent decline at recovery in both subgroups of patients, with the most pronounced decrease in the NO group. cGMP concentrations increased significantly only in the NO group, with a peak at 1 hour of treatment (median, 61 pmol/ml). As the dose of NO decreased, cGMP concentrations declined. In contrast, conventionally treated infants manifested no change in cGMP concentrations from baseline until recovery, when a significant decrease was noted (median decrease of 13 pmol/ml; p = 0.002). We did not find a significant difference between ET-1 and cGMP concentrations in infants who required extracorporeal membrane oxygenation compared with those who did not. CONCLUSIONS: PPHN is associated with increased ET-1 and decreased cGMP plasma concentrations, which may contribute to the pathogenesis of the disease. Inhaled NO appears to modulate these mediators during the disease process, suggesting an interaction between ET-1 and NO in vivo.
Assuntos
GMP Cíclico/sangue , Endotelina-1/sangue , Óxido Nítrico/administração & dosagem , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Administração por Inalação , Feminino , Humanos , Recém-Nascido , Masculino , Óxido Nítrico/fisiologia , Síndrome da Persistência do Padrão de Circulação Fetal/sangueRESUMO
Meconium, an ether extract of meconium, and the major free fatty acids of meconium (palmitic, stearic, and oleic acids) were all found to increase the surface tension minimum of dog lung extract in a Wilhelmy balance. Each of these fractions was instilled into the lungs of dogs (15 experimental, eight saline solution controls), and cardiac output, venous and arterial blood gases, pulmonary, atrial, and systemic pressures, airway pressure, and static lung compliance were serially monitored for 2 hours. Mean airway pressure increased and static lung compliance decreased significantly in all of the experimental groups. Although arterial pH and PaCO2 and the various hemodynamic measurements did not change during the experiment, PaO2 decreased significantly and did not return to baseline in all experimental groups. Extracts from atelectatic portions of experimental dog lung had a surface tension minimum of greater than 20 dynes/cm, whereas airway foam had a surface tension minimum of less than 10 dynes/cm, suggesting that the free fatty acids of meconium are able to strip surfactant from the alveoli.
Assuntos
Ácidos Graxos não Esterificados/farmacologia , Mecônio , Pneumonia Aspirativa/complicações , Atelectasia Pulmonar/etiologia , Surfactantes Pulmonares , Animais , Cães , Humanos , Recém-Nascido , Pneumonia Aspirativa/fisiopatologia , Tensão SuperficialRESUMO
The continued influx of immigrants from Mexico, Central America, and Southeast Asia to the United States has resulted in an increased incidence of several diseases not generally seen in industrialized nations in the twentieth century. One of these is amebic abscess of the liver. This review of the diagnostic features of 57 patients with amebic abscess of the liver treated in one Los Angeles County hospital emphasizes the diagnosis and the versatility of the various roentgenologic approaches and serologic tests.