RESUMEN
High-frequency oscillatory ventilation (HFOV) has been proposed as an alternative method of invasive ventilation in immature infants to prevent ventilator lung injury. To better control the size of the high-frequency tidal volume and to prevent large tidal volumes, a new strategy of controlling the tidal volume during HFOV (VThf) has been developed, HFOV-volume guarantee (VG). Data from preclinical, neonatal animal studies in normal and surfactant-depleted lungs have demonstrated the feasibility of this technique to directly control the VThf in the normal compliance and low compliance situations. Different I:E ratios also can modify the effect of CO2 washout during HFOV combined with VG in a different way as without the VG modality. Finally, clinical use of this technique in newborn infants has demonstrated the possibility of using very high frequency combined with constant very low VThf to decrease the risk of lung trauma related to the ventilator.
Asunto(s)
Ventilación de Alta Frecuencia/métodos , Ventilación con Presión Positiva Intermitente/métodos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Volumen de Ventilación Pulmonar , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Humanos , Recién Nacido , Recien Nacido Prematuro , Pulmón/irrigación sanguínea , Pulmón/fisiopatología , Intercambio Gaseoso PulmonarRESUMEN
Endoglin is a TGF-beta superfamily receptor critical for endothelial cell function. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia type I (HHT1), and clinical signs of disease are generally more evident later in life. We previously showed that systemic vessels of adult Eng heterozygous (Eng(+/-)) mice exhibit increased vasorelaxation due to uncoupling of endothelial nitric oxide synthase (eNOS). We postulated that these changes may develop with age and evaluated pulmonary arteries from newborn and adult Eng(+/-) mice for eNOS-dependent, acetylcholine (ACh-induced) vasorelaxation, compared with that of age-matched littermate controls. While ACh-induced vasorelaxation was similar in all newborn mice, it was significantly increased in the adult Eng(+/-) vs. control vessels. The vasodilatory responses were inhibited by l-NAME suggesting eNOS dependence. eNOS uncoupling was observed in lung tissues of adult, but not newborn, heterozygous mice and was associated with increased production of reactive O(2) species (ROS) in adult Eng(+/-) vs. control lungs. Interestingly, ROS generation was higher in adult than newborn mice and so were the levels of NADPH oxidase 4 and SOD 1, 2, 3 isoforms. However, enzyme protein levels and NADPH activity were normal in adult Eng(+/-) lungs indicating that the developmental maturation of ROS generation and scavenging cannot account for the increased vasodilatation observed in adult Eng(+/-) mice. Our data suggest that eNOS-dependent H(2)O(2) generation in Eng(+/-) lungs accounts for the heightened pulmonary vasorelaxation. To the extent that these mice mimic human HHT1, age-associated pulmonary vascular eNOS uncoupling may explain the late childhood and adult onset of clinical lung manifestations.
Asunto(s)
Envejecimiento/metabolismo , Heterocigoto , Péptidos y Proteínas de Señalización Intracelular/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Arteria Pulmonar/enzimología , Envejecimiento/efectos de los fármacos , Animales , Animales Recién Nacidos , Fenómenos Biomecánicos/efectos de los fármacos , Endoglina , Células Endoteliales/efectos de los fármacos , Células Endoteliales/enzimología , Proteínas HSP90 de Choque Térmico/metabolismo , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Inmunoprecipitación , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Pulmón/efectos de los fármacos , Pulmón/enzimología , Ratones , NADPH Oxidasas/metabolismo , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Tomografía Computarizada por Rayos X , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Gastric residuals are a common finding in enterally fed preterm neonates and traditionally thought to reflect immaturity-related delayed gastric emptying. Adult human data suggest that the meal volume regulate the gastric emptying rate, but early in life, this has not been adequately evaluated. The goal of this study was to study the rat postnatal changes in gastric emptying rate and the strain-induced effect on muscle contraction. We hypothesized that the stomach content volume and not developmental factors determines the newborn gastric emptying rate, via the Rho-kinase 2 (ROCK-2) pathway. METHODS: Gastric volume and emptying rate measurements were obtained by ultrasound at different postprandial times and the wall strain-dependent changes in muscle contraction were evaluated ex vivo. KEY RESULTS: The newborn rat gastric emptying rate was unrelated to postnatal age, maximal 30 min postprandial, and directly proportional to content volume. In vitro measurements showed that the agonist-induced gastric muscle contraction was directly proportional to the stomach wall strain. These changes were mediated via upregulation of ROCK-2 activity. CONCLUSIONS & INFERENCES: The newborn rat gastric emptying rate is not developmentally regulated, but dependent on the content volume via wall strain-induced ROCK-2 activation. Further clinical studies addressing the content volume effect on the rate of gastric emptying are warranted, to enhance feeding tolerance in preterm neonates.
Asunto(s)
Vaciamiento Gástrico , Estómago/fisiología , Animales , Animales Recién Nacidos/fisiología , Femenino , Mucosa Gástrica/metabolismo , Masculino , Contracción Muscular , Periodo Posprandial , Ratas Sprague-Dawley , Estómago/crecimiento & desarrollo , Quinasas Asociadas a rho/metabolismoRESUMEN
OBJECTIVE: The objective of this study was to evaluate carbon dioxide (CO2) clearance, delivered pressures and tidal volume (VT) during neonatal nasal intermittent positive pressure ventilation (NIPPV) with two commonly used interfaces. STUDY DESIGN: A neonatal lung model, with either short binasal prongs (SBP) or a small caliber nasal cannula (RAM) interface, was tested over a range of clinically relevant settings. A fixed amount of CO2 was infused and the fraction remaining in the lung 100 s postinfusion was measured. Pressure transmission to the lung and VT was measured at the level of the trachea. RESULT: CO2 elimination was directly proportional to the inspiratory pressure during NIPPV. At peak pressures of 22 to 34 cm H2O, CO2 clearance was greater (P<0.001) with SBP as compared with RAM. Relative to the set ventilator parameters, a substantial pressure dampening effect was documented at the lung level, which was significantly lower with RAM when compared with SBP (2.8% (0.2) versus 11.9% (1.5), P<0.0001). CO2 elimination was dependent on VT and effective despite only a small fraction of physiological VT (maximum delivered VT%: SBP 15.5 (0.7) versus RAM 6.1 (1.4), P<0.0001). CONCLUSION: NIPPV promotes CO2 elimination even at low transmitted airway pressures, but less effective with RAM as compared with SBP. CO2 elimination despite small VT suggests that NIPPV may depend on a non-conventional gas-exchange mechanism.
Asunto(s)
Dióxido de Carbono/análisis , Enfermedades del Recién Nacido/terapia , Ventilación con Presión Positiva Intermitente , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control , Humanos , Recién Nacido , Ventilación con Presión Positiva Intermitente/efectos adversos , Ventilación con Presión Positiva Intermitente/métodos , Maniquíes , Intercambio Gaseoso Pulmonar/fisiología , Volumen de Ventilación Pulmonar/fisiología , Ventiladores Mecánicos/efectos adversos , Ventiladores Mecánicos/normasRESUMEN
A patient with recurrent vomiting, abdominal pain, and elevated serum amylase activity may have pancreatitis. Although elevated serum amylase levels are a sensitive indicator for acute pancreatitis, this test is not highly specific for pancreatic disease. A patient is described who illustrates the need for specific laboratory, historical, and occasional psychological evaluation in pediatric patients with elevated amylase values.
Asunto(s)
Amilasas/sangre , Esquizofrenia/complicaciones , Sialorrea/complicaciones , Abdomen , Adolescente , Diagnóstico Diferencial , Humanos , Isoenzimas/sangre , Masculino , Dolor/etiología , Pancreatitis/diagnóstico , Esquizofrenia/sangre , Sialorrea/sangre , Vómitos/etiologíaRESUMEN
The effect of a progressive increase in right ventricular (RV) afterload was studied in pigs less than 24 h (group I) and 3-5 days old (group III). RV load was applied to increase mean pulmonary arterial pressure (Ppa) until right to left shunt was observed. Initially, pigs in group I had a significantly lower systemic arterial pressure (Psa = 63 +/- 2 vs. 82 +/- 5 mmHg) and higher Ppa (30 +/- 1 vs. 23 +/- 2 mmHg) even though the RV stroke work (RVSW) was similar (54.3 +/- 10.8 vs. 32.4 +/- 2.1 mmHg/ml) to group II. After a progressive rise in afterload, pigs in group I could maintain a higher RV stroke volume than those in group II (1.3 +/- 0.3 vs. 0.4 +/- 0.1 ml; P less than 0.05). At shunt condition, the RVSW was increased by 21 +/- 14% of the initial value in group I vs. a 32 +/- 8% decrease in group II (P less than 0.05). The ductus arteriosus was constricted and right-to-left shunt was observed in all animals at the foramen ovale level even though Ppa exceeded Psa before the rise in the right atrial pressure in group I. Thus, as RV afterload is increased in the pig, the older animals' right ventricle is progressively less capable of maintaining pulmonary blood flow than animals within 24 h of birth.
Asunto(s)
Corazón/fisiopatología , Hemodinámica , Hipertensión Pulmonar/fisiopatología , Animales , Animales Recién Nacidos , Presión Sanguínea , Ventrículos Cardíacos/fisiopatología , Circulación Pulmonar , Volumen Sistólico , Porcinos , Resistencia VascularRESUMEN
The objective of this study was to evaluate the in vitro effect of budesonide and salbutamol on the surfactant biophysical properties. The surface-tension properties of two bovine lipid extracts [bovine lipid extract surfactant (BLES) and Survanta] and a rat lung lavage natural surfactant were evaluated in vitro by the captive bubble surfactometer. Measurements were obtained before and after the addition of a low and high concentration of budesonide and salbutamol. Whereas salbutamol had no significant effect, budesonide markedly reduced the surface-tension-lowering properties of all surfactant preparations. Surfactant adsorption (decrease in surface tension vs. time) was significantly reduced (P < 0.01) at a high budesonide concentration with BLES, both concentrations with Survanta, and a low concentration with natural surfactant. At both concentrations, budesonide reduced (P < 0.01) Survanta film stability (minimal surface vs. time at minimum bubble volume), whereas no changes were seen with BLES. The minimal surface tension obtained for all surfactant preparations was significantly higher (P < 0.01), and the percentage of film area compression required to reach minimum surface tension was significantly lower after the addition of budesonide. In conclusion, budesonide, at concentrations used therapeutically, adversely affects the surface-tension-lowering properties of surfactant. We speculate that it may have the same adverse effect on the human surfactant.
Asunto(s)
Albuterol/farmacología , Antiinflamatorios/farmacología , Productos Biológicos , Broncodilatadores/farmacología , Budesonida/farmacología , Surfactantes Pulmonares/efectos de los fármacos , Surfactantes Pulmonares/fisiología , Administración Tópica , Adsorción , Animales , Femenino , Glucocorticoides , Masculino , Concentración Osmolar , Ratas , Ratas Sprague-Dawley , Tensión Superficial/efectos de los fármacosRESUMEN
To evaluate the maturational changes in vascular muscle mechanics we studied and compared the isotonic half-time relaxation (t1/2P,CE) and maximal load-bearing capacity normalized to stress of pulmonary and systemic arterial muscle from perinatal and adult sheep. For the pulmonary and systemic vessels t1/2P,CE was significantly shorter in adult than in perinatal sheep (P < 0.01). In newborns t1/2P,CE of the pulmonary vessels was 185 +/- 31 (SE) s, longer than that of the systemic vessels (64 +/- 10 s; P < 0.01). In adults t1/2P,CE of the pulmonary vessels (101 +/- 14 s) was longer than that of the systemic vessels (37 +/- 5 s; P < 0.01). Maximal load-bearing capacities normalized to stress of pulmonary vessels of fetal and newborn sheep were twofold greater than those of adult sheep and of the systemic vessels of newborns and adults (P < 0.01). In conclusion, significant maturational changes in the isotonic and isometric mechanical properties of vascular pulmonary and systemic smooth muscle were observed in sheep.
Asunto(s)
Arterias Carótidas/fisiología , Músculo Liso Vascular/fisiología , Circulación Pulmonar/fisiología , Envejecimiento/fisiología , Animales , Animales Recién Nacidos/fisiología , Endotelio Vascular/fisiología , Femenino , Técnicas In Vitro , Contracción Isométrica/fisiología , Contracción Isotónica/fisiología , Contracción Muscular/fisiología , Relajación Muscular/fisiología , Embarazo , OvinosRESUMEN
To evaluate the developmental changes in pulmonary vascular smooth muscle contractile protein content, mechanical properties, and their contribution to the high resistance characteristic of the fetal and immediate neonatal period, we studied pulmonary vessels of fetal, newborn, and adult sheep, as well as newborn and adult pigs. Strips of the second- through fifth-generation vessels were dissected, and their content of tissue total smooth muscle cell protein, myosin, and actin-to-myosin ratio were measured; the mechanical properties of the second-generation vascular strips were also studied. For all ages the smooth muscle protein and myosin content of the second-generation vessels were significantly greater than for the lower pulmonary vascular orders (P less than 0.05). The myosin content in fetal sheep (0.77 +/- 0.03 micrograms/mg wet tissue) was similar to that of the newborn (0.79 +/- 0.04) and adult (0.86 +/- 0.05). However, the smooth muscle protein content (7.94 +/- 0.21 micrograms/mg wet tissue) and the actin-to-myosin ratio of the pulmonary vascular tissue of the fetus (1.00 +/- 0.04) were lower (P less than 0.01) in the fetal than in the newborn (9.16 +/- 0.26 and 1.60 +/- 0.12) and adult (9.38 +/- 0.3 and 1.60 +/- 0.11, respectively). No differences were observed for these parameters between the newborn and adult pig. Stress (16.5 +/- 1.7 mN/mm2) and the maximum shortening capacity (13.0 +/- 1.5% of optimal length) in the newborn pulmonary vascular strips were significantly greater than for the fetus (6.8 +/- 1.4 and 5.9 +/- 1.0, respectively) but similar to those of the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Pulmón/fisiología , Músculo Liso Vascular/fisiología , Circulación Pulmonar/fisiología , Actinas/metabolismo , Animales , Animales Recién Nacidos/fisiología , Fenómenos Biomecánicos , Endotelio Vascular/fisiología , Femenino , Feto/fisiología , Contracción Isométrica/fisiología , Contracción Isotónica/fisiología , Pulmón/crecimiento & desarrollo , Pulmón/metabolismo , Proteínas Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Miosinas/metabolismo , Embarazo , Ovinos , PorcinosRESUMEN
The present study investigates the integrity of the blood-brain barrier to H+ or HCO3- during acute plasma acidosis in 35 newborn piglets anesthetized with pentobarbital sodium. Cerebrospinal fluid acid-base balance, cerebral blood flow (CBF), and cerebral oxygenation were measured after infusion of HCl (0.6 N, 0.191-0.388 ml/min) for a period of 1 h at a constant arterial PCO2 of 35-40 Torr. HCl infusion resulted in decreased arterial pH from 7.38 +/- 0.01 to 7.00 +/- 0.02 (P less than 0.01). CBF measured by the tracer microsphere technique was decreased by 12% from 69 +/- 6 to 61 +/- 4 ml.min-1.100 g-1 (P less than 0.05). Infusion of 0.6 N NaCl as a hypertonic control had no effect on CBF. Cerebral metabolic rate for O2 and O2 extraction was not significantly changed from control (3.83 +/- 0.20 ml.min-1.100 g-1 and 5.7 +/- 0.6 ml/100 ml, respectively) during acid infusion. Cerebral venous PO2 was increased from 41.6 +/- 2.1 to 53.8 +/- 4.0 Torr by HCl infusion (P less than 0.02) associated with a shift in O2-hemoglobin affinity of blood in vivo from 38 +/- 2 to 50 +/- 1 Torr. Cisternal cerebrospinal fluid pH decreased from 7.336 +/- 0.014 to 7.226 +/- 0.027 (P less than 0.005), but cerebrospinal fluid HCO3- concentration was not changed from control (25.4 +/- 1.0 meq/l). These data suggest that there is a functional blood-brain barrier in newborn piglets, that is relatively impermeable to HCO3- or H+ and maintains cerebral perivascular pH constant in the face of acute severe arterial acidosis. (ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Acidosis/metabolismo , Barrera Hematoencefálica , Protones , Equilibrio Ácido-Base , Animales , Animales Recién Nacidos , Bicarbonatos/sangre , Bicarbonatos/líquido cefalorraquídeo , Presión Sanguínea , Dióxido de Carbono/sangre , Dióxido de Carbono/líquido cefalorraquídeo , Circulación Cerebrovascular/efectos de los fármacos , Ácido Clorhídrico/farmacología , Concentración de Iones de Hidrógeno , Oxígeno/sangre , Oxígeno/líquido cefalorraquídeo , PorcinosRESUMEN
Neonatal rats exposed to 60% O(2) for 14 days develop lung changes compatible with human bronchopulmonary dysplasia and pulmonary hypertension. Our aim was to evaluate and compare the newborn and adult rat pulmonary vascular and airway smooth muscle force generation and relaxation potential after exposure to 60% O(2) for 14 days. Vascular and airway intrapulmonary rings 100 microm in diameter were mounted on a myograph and bathed in Krebs-Henseleit solution bubbled with air- 6% CO(2) at 37 degrees C. Significant age-dependent changes in intrapulmonary arteries and their neighboring airway muscle properties were observed. Whereas hyperoxia enhanced force in neonatal vascular and airway muscle, the opposite was seen in adult samples. No changes in endothelium-dependent vascular relaxation were observed at either age, but the dose response to an endothelium-independent NO donor was altered. In the newborn experimental animals, the relaxation was reduced, whereas, in their adult counterparts, it was enhanced. After O(2) exposure, the bronchial muscle relaxation response to epithelium-dependent and -independent stimulation was not altered in either age group, whereas the epithelium-dependent response was decreased only in the adult. The antioxidant Trolox, or an endothelin-A and -B receptor antagonist, reversed the vascular and airway muscle's hyperoxia-induced changes. We conclude that chronic O(2) exposure in the newborn rat results in enhanced lung vascular and airway muscle contraction potential via a mechanism involving reactive oxygen species and the endothelin pathway. The present findings also suggest that the newborn is more susceptible to airway hyperresponsiveness after chronic O(2) exposure.
Asunto(s)
Animales Recién Nacidos/fisiología , Hiperoxia/fisiopatología , Pulmón/fisiopatología , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiopatología , Arteria Pulmonar/fisiopatología , Vasoconstricción/efectos de los fármacos , Envejecimiento/fisiología , Animales , Enfermedad Crónica , Femenino , Relajación Muscular , Músculo Liso Vascular/fisiopatología , Ratas , Ratas Sprague-Dawley , VasodilataciónRESUMEN
The factors accounting for the maintenance of a low pulmonary vascular resistance postnatally are not completely understood. The aim of this study was to test the hypothesis that bronchial epithelium produces a factor capable of relaxing adjacent pulmonary arterial smooth muscle. We studied fourth-generation intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were mounted on a wire myograph, alone or with the adjacent bronchus. The presence of the attached bronchus significantly reduced pulmonary artery force generation induced by the thromboxane analog (U-46619) or KCl whether the endothelium was present or absent (P < 0.01). The converse was not true in that bronchial force generation was not affected when studied with the adjacent pulmonary artery. Mechanical removal of the bronchial epithelium or addition of the nitric oxide (NO) synthase (NOS) nonspecific (N(G)-monomethyl-l-arginine) or the specific neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to levels comparable to the isolated artery preparation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, significantly decreased (P < 0.01) NO release of pulmonary arteries only when the adjacent bronchus was present. We conclude that bronchial epithelium in the newborn rat produces a factor capable of lowering pulmonary vascular muscle tone. This relaxant effect can be suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting an action via NOS phosphorylation and NO release. We speculate that such a mechanism may be operative in vivo and plays an important role in control of pulmonary vascular resistance in the early postnatal period.
Asunto(s)
Animales Recién Nacidos/fisiología , Bronquios/metabolismo , Arteria Pulmonar/fisiología , Vasodilatación/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Androstadienos/farmacología , Animales , Inhibidores Enzimáticos/farmacología , Epitelio/metabolismo , Técnicas In Vitro , Indazoles/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Inhibidores de las Quinasa Fosfoinosítidos-3 , Cloruro de Potasio/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Wortmanina , omega-N-Metilarginina/farmacologíaRESUMEN
8-Isoprostaglandin F2alpha (8-iso-PGF2alpha) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF2alpha responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2alpha effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 microm) mounted on a myograph. Force after 8-iso-PGF2alpha stimulation was greatest in the adult (P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2alpha induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 microM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2alpha-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2alpha induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult (P < 0.01). When exposed to 8-iso-PGF2alpha in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2alpha induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.
Asunto(s)
Prostaglandinas A/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Factores de Edad , Animales , Animales Recién Nacidos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Inhibidores Enzimáticos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas Sprague-Dawley , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2a)) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF(2alpha) may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF(2a) induced a significantly greater force (P < 0.01) and reduced (P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-L-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased (P < 0.01) in the experimental group. Pulmonary (P < 0.05) and aortic (P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF(2alpha)-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.
Asunto(s)
Hiperoxia/metabolismo , Hipertensión Pulmonar/metabolismo , Músculo Liso Vascular/fisiología , Óxido Nítrico/metabolismo , Arteria Pulmonar/metabolismo , Animales , Animales Recién Nacidos , Enfermedad Crónica , Dinoprost/análogos & derivados , Dinoprost/farmacología , Femenino , Hiperoxia/fisiopatología , Hipertensión Pulmonar/fisiopatología , Isoprostanos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Oxígeno/farmacología , Embarazo , Ratas , Ratas Sprague-Dawley , Vasoconstrictores/farmacologíaRESUMEN
To determine the natural history of lung vascular remodeling and cardiac changes in the rat model of persistent pulmonary hypertension syndrome (PPHN) of the newborn, we studied fetal rats subjected to maternal indomethacin administration initiated on day 19 of gestation and continued for 2, 3, or 4 days. Animals receiving a similar volume of water or alcohol served as controls. Significant pulmonary hypertension was noted in the experimental group, as evidenced by a significantly increased right to left ventricular wall ratio to 1.6 +/- 0.1 in the 4-day treatment group, as compared with 1.2 +/- 0.4 in the control group (P < 0.01). The smooth muscle area for <25 microm external diameter arterial vessels was significantly increased (12.7 +/- 0.6 vs. 10.0 +/- 0.6 microm; P < 0.01) and the adventitial area of all diameters vessels was significantly greater (P < 0.01) following 3 days of indomethacin treatment, as compared with water controls. Associated with these changes, the 4-day treatment group's lung/body weight ratio was 0.021 +/- 0.001, and was significantly less (P < 0.01) than for the control group (0.035 +/- 0.001). This reduction in lung weight was not associated with changes in lung protein content or wet/dry weight ratio, indicating that pulmonary hypertension in the fetal rat induced lung hypoplasia. In conclusion, closure of the ductus arteriosus in the fetal rat results in early-onset right ventricular hypertrophy, followed by pulmonary vascular remodeling and lung hypoplasia. We speculate that lung growth in late gestation is adversely affected by pulmonary hypertension.
Asunto(s)
Corazón Fetal/patología , Corazón Fetal/fisiopatología , Hipertensión Pulmonar/fisiopatología , Pulmón/fisiopatología , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Femenino , Hipertensión Pulmonar/inducido químicamente , Indometacina/efectos adversos , Pulmón/patología , Embarazo , RatasRESUMEN
The effect of early furosemide-induced diuresis was prospectively evaluated in 39 neonates less than 24 hr of age with clinical respiratory distress syndrome (RDS) who received either four doses of furosemide (1 mg/kg) or no diuretic. Measurements of FiO2 alveolar-arterial oxygen gradient (P[A-a]O2), peak inspiratory pressure (PIP), and urine output as a fraction of intake (O/I) were averaged for every 8 hr. The furosemide group overall showed a significant decrease (P less than 0.01) in FiO2, P[A-a]O2, and PIP with an earlier (32 hr vs 52 hr) and more pronounced diuresis (35% greater O/I) when compared to the controls. This effect was accentuated in the subgroup with 1,000-1,500 g birth weight (significantly lower FiO2 and P(A-a)O2 from 16 to 48 hours), while no increase in urine output was observed for the infants weighing less than 1,000 g. A significant reduction in supplemental oxygen and need for ventilatory support at 96 hr of age was observed in the furosemide-treated, less than 1,500-g infants. The incidence of patent ductus arteriosus was not increased following furosemide therapy, and no significant difference in echocardiographic parameters was observed in 21 infants from both groups, who were followed daily during the first week of life. This study suggests that early furosemide-induced diuresis, particularly in infants weighing 1,000-1,500 g at birth, promotes improvement in pulmonary functions in RDS and leads to faster reduction in oxygen and ventilatory support.
Asunto(s)
Furosemida/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Peso al Nacer , Diuresis , Humanos , Recién Nacido , Estudios Prospectivos , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Factores de TiempoRESUMEN
Metatropic dwarfism is a rare heritable skeletal dysplasia that is thought to result from a defect in endochondral ossification. Histological studies have been few and have yielded inconsistent findings. In addition, no investigator has commented on the structure and function of the perichondral portion of the growth plate in patients who have metatropic dysplasia. To further characterize this disturbance, histological studies were carried out on autopsy specimens from the proximal part of the femur and the iliac crest of a patient who had this disorder. The major findings were: the absence of formation of normal primary spongiosa in the metaphysis; the presence of a thin seal of bone at the chondro-osseous junction, with abnormal metaphyseal vascular invasion and arrest of endochondral growth; and normal-appearing perichondral ring structures with persistence of circumferential growth. These findings suggest an uncoupling of endochondral and perichondral growth and offer an explanation for the dumbbell-shaped morphological structure of the osseous metaphysis that is seen in patients who have metatropic dysplasia. Other observations included prominence of the cartilaginous canals and vascular channels in the reserve zone; clumping of chondrocytes with enhanced staining of the pericellular matrix in the proliferative zone; a decreased ratio of cells to matrix in the hypertrophic zone, with intracellular metachromatic granules and incomplete evolution of chondrocytes; complete absence of an alcian-blue-positive zone of provisional calcification; and, finally, islands of dysplastic chondrocytes in the metaphysis. These abnormalities suggest that metatropic dysplasia is not simply a disorder of endochondral ossification. There appear to be associated defects in the longitudinal proliferation and maturation of chondrocytes and in the production of normal matrix.
Asunto(s)
Acondroplasia/patología , Placa de Crecimiento/patología , Acondroplasia/diagnóstico por imagen , Humanos , Lactante , Masculino , Huesos Pélvicos/diagnóstico por imagen , Radiografía , Columna Vertebral/diagnóstico por imagenRESUMEN
Lithium is widely used and the treatment of choice for patients with manic-depressive illness. For pregnant patients with manic-depressive illness, however, the use of lithium during the first trimester of pregnancy may present an increased risk for fetal maldevelopment. We have recently cared for several large-for-gestational-age, prematurely born infants whose mothers were treated with lithium throughout pregnancy. To determine whether maternal lithium use during pregnancy may predispose to the onset of premature labor and fetal macrosomia, we reviewed records from the International Register of Lithium Babies and from a cohort of manic-depressive pregnant women. More than one third (36%) of infants reported to the International Register were born prematurely, and 37% of the premature infants were large for gestational age; 15% of the term infants were born large for gestational age. In the cohort group, manic-depressive mothers who received lithium during pregnancy had a 2.5-fold higher incidence of premature births than manic-depressive pregnant patients who did not receive lithium treatment. The incidence of large-for-gestational-age births in lithium-treated women in the cohort was not different from that of the general population or from manic-depressive women not treated with lithium. In summary, an association between maternal lithium therapy and premature delivery is reported. We recommend that women receiving lithium therapy during pregnancy be closely monitored for the onset of premature labor.
Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Macrosomía Fetal/inducido químicamente , Litio/efectos adversos , Trabajo de Parto Prematuro/inducido químicamente , Complicaciones del Embarazo/tratamiento farmacológico , Adulto , Peso al Nacer/efectos de los fármacos , Distribución de Chi-Cuadrado , Estudios de Cohortes , Desarrollo Embrionario y Fetal/efectos de los fármacos , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Litio/uso terapéutico , Edad Materna , Intercambio Materno-Fetal , Embarazo , Estudios RetrospectivosRESUMEN
Two infants with clinical and radiologic features of metatropic dwarfism presented in the neonatal period with episodes of cyanosis. Diagnostic studies to determine the etiology of these spells, including electrocardiogram, electroencephalogram, arterial blood gases, and metabolic and sepsis studies, were unremarkable. Chest roentgenograms revealed the characteristic long, narrow thoracic cage with no evidence of parenchymal disease. Cervical spine stability evaluation, pulmonary function studies, and chest impedance monitoring with qualitative air flow thermistor studies and transcutaneous oxygen monitoring were carried out. Both patients demonstrated a significant increase in resistance of the respiratory system following passive maneuvering of the head from a neutral position, suggestive of hypopharyngeal air flow obstruction. Obstructive sleep apnea resulting in cyanosis was documented in both patients. All other studies failed to yield a cause for the episodes of cyanosis. Our investigation failed to alter the clinical course which resulted in respiratory arrest and death by 7 months of age. A table is presented for the differentiation of skeletal dysplasias presenting in the perinatal period.
Asunto(s)
Enanismo/complicaciones , Insuficiencia Respiratoria/etiología , Vértebras Cervicales/diagnóstico por imagen , Cianosis/etiología , Enanismo/diagnóstico por imagen , Enanismo/fisiopatología , Humanos , Lactante , Masculino , Monitoreo Fisiológico , Enfermedad Cardiopulmonar/etiología , Radiografía , Pruebas de Función Respiratoria , Síndromes de la Apnea del Sueño/etiologíaRESUMEN
OBJECTIVE: To examine the role of frequency in high-frequency ventilation (HFV) on carbon-dioxide (CO2) elimination and lung injury, independent of its effect on tidal volume. STUDY DESIGN: An anatomically representative lung model was attached to a mechanical ventilator capable of providing HFV with a constant volume. CO2 was infused directly into the lung, and a commercially available end-tidal CO2 detector was used to determine CO2 elimination. CO2 elimination and amplitude of pressure transmissions were evaluated using frequencies ranging from 5 to 15 Hz. The pressure-volume index (PVI) was described as the product of the volume and pressures delivered to the lung, a surrogate for lung injury. RESULT: The use of increasing frequencies directly correlated with improved CO2 clearance when keeping the tidal volume fixed, expressed as percent CO2 remaining in the lung at 25 s (66.5 (±1.1)%, 50.5 (±0.1)% and 37.8 (±0.3)% at 5, 10 and 15 Hz, respectively, P<0.05). With a fixed tidal volume, there was a decrease in pressure amplitudes transmitted to the lung with a decline in the PVI (53.9 (±2.7) mmHg ml(-1), 41.1 (±0.9) mmHg ml(-1) and 23.4 (±3.6) mmHg ml(-1), at 5, 10 and 15 Hz, respectively, P<0.05). CONCLUSION: Frequency has a direct relationship with CO2 elimination when tidal volume is fixed. Using low delivered tidal volumes and high frequencies may allow for improved ventilation efficacy, while minimizing lung injury.