摘要:

Neonatal rats were treated with low doses of bacterial ipopolysaccharide (endotoxin) to test for a protective effect of endotoxin against O2toxicity and the severe inhibition of normal lung development which occurs during prolonged exposure to hyperoxia. The rationale for the prophylactic use of endotoxin included its marked protective effect against pulmonary O2toxicity in adult rats and its lung growth-promoting effect in experimental pulmonary stress models. Neonatal rats (4-5 days old) survived a 14-day exposure to >95% O2equally well whether treated with saline (39/51=76%) or with endotoxin (41/51=80%). However, during the following 24 h of gradual weaning to room air breathing, there was a marked difference in survival between the endotoxin group (32/41=78%) and the saline pups (14/39=36%) (p<0.001). Both groups showed inhibition of lung development (alveolarization) during O2exposure, but endotoxin treatment compared to saline was associated with increased specific lung volume (5.33 versus 4.50 ml/100 g) (air control=4.08), smaller mean airspace diameter (mean linear intercept=49.0 versus 55.8 μm) (air control=43.3), increased specific internal surface area (4393 versus 3232 cm2/100 g) (air control=3753), and greater preservation of alveolar wall capillary patency (24.83 versus 18.52% “capillary density”) (air control=27.70%). We conclude that endotoxin treatment resulted in significant protection against O2toxicity in neonatal rats which was manifested during readaptation to room air breathing. The protective effect was likely due to a combination of reduced inhibition of lung growth and development and reduced hyperoxic damage to the respiratory membrane of the lung.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Experiments were done to investigate the effects of increased inspired oxygen on the arousal response from sleep to upper airway obstruction in 10 newborn lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of systemic arterial blood pressure and oxygen saturation (fiberoptic catheter oximeter). A tracheotomy was performed and a fenestrated tracheostomy tube was placed in the trachea. A 5F balloon tipped catheter was inserted into the tube so that airflow could be obstructed by inflating the balloon. No sooner than 3 days after surgery, measurements were made during a control period and during an experimental period of upper airway obstruction; the inspired oxygen fraction was alternated hourly between 0.21 and 0.60. A total of 57 epochs of quiet sleep and 58 epochs of active sleep was obtained in eight lambs. Arousal was significantly delayed (p < 0.005) during active sleep (21 ± 6 s; mean ± 1 SD) compared to quiet sleep (7 ± 2 s) in room air. Increased inspired oxygen significantly delayed arousal (p < 0.05) during active sleep (47 ± 25 s), but had little effect on arousal in quiet sleep (10 ± 4 s). These results provide evidence that arousal from active sleep following upper airway obstruction in lambs is primarily initiated by a decrease in arterial oxygen. However, arousal from quiet sleep following upper airway obstruction in lambs appears to be initiated by other stimuli.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The diaphragmatic force generation and electromyographic response to long-term (1 h) inspiratory resistive loading was examined in the newborn piglet during the 3rd postnatal wk of life. Minute ventilation decreased to approximately 50% of baseline level within 5 min of imposition of a severe resistive load and remained at this level for the duration of loading. The decrease in ventilation was secondary to a fall in tidal volume at a constant frequency. There was a significant increase in central nervous system output to the diaphragm as manifested by integrated diaphragmatic electromyogram. Progressive augmentation of this index of central drive continued throughout the period of loading. Functional residual capacity fell significantly by 60 min of inspiratory resistive loading. This strategy should allow greater force generation by placing the diaphragm at a more optimal length-tension relationship. However, the force generating capability of the diaphragm was compromised as assessed by force frequency curve analysis. These results suggest that the diaphragm of the neonatal piglet fatigues during prolonged inspiratory resistive loading.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effects of the aqueous phase of human breast milk on the disaccharidase activity of newborn rabbit small intestinal mucosal explants were studied in vitro culture. These explants continuously synthesized protein and normal morphology was maintained for the duration of the cultures. Addition of the aqueous phase resulted in significant increase of lactase (p / 0.001) and maltase (p /0.01) concentrations in these organ cultures. This effect was dose dependent and was observed whether the organ biopsies were derived from fed or starved newborn rabbits. Further purification of the aqueous phase showed that the active ingredient exerting these effects was lactose. These studies suggest that lactose may have an important function in stabilization of newborn intestinal disaccharidase enzymes.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the Iamb. We studied eight unanesthetized newborn lambs (mean age 7 ± 2 days) during a 15-inin baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 μg/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclidelabeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 μg/kg/min but decreased at 160 μg/ kg/ min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 μg/ kg/ min. Blood flow to all organs was unchanged at the 5 μg/ kg/ min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 μg/ kg/ min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Deficiency of purine nucleoside phosphorylase (PNP) was detected in a 3-yr-oId boy who was admitted for investigation of a behavior disorder and spastic diplegia. The urinary excretion of purines, analyzed by high-performance liquid chromatography, showed the presence of large amounts of (deoxy)inosine and (deoxy)guanosine and low uric acid levels. Analysis of the (deoxy)nucleotide pools of erythrocytes showed elevated levels of deoxyguanine nucleotides and NAD and decreased guanine nucleotides. PNP activity in red blood cells was 0.1-0.5% of normal on two occasions and undetectable on four later measurements. Furthermore no immunoreactive material could be detected in his red cell lysate using an anti-PNP antiserum. PNP activities in the red cells of the patient's parents were 35 and 50% of normal. The presence of (minor) residual PNP activity in the patient enabled the investigation of some enzyme properties after partial purification. No abnormalities could be detected in substrate affinity for inosine, heat stability, and electrophoretic properties. In the heterozygous parents no signs of a mutant enzyme could be found. The molecular specific activities of the parental enzymes were also normal, indicating that no immunoreactive material attributable to inactive-mutant enzyme subunits was present. A striking feature of the patient is the prevailing neurologic abnormalities presumably caused by the metabolic disorder. A severe lymphopenia exists; however, clinical symptoms of an immune deficiency did not become apparent until the age of 4 yr.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We designed experiments to determine whether β-adrenergic receptors are present and functional in human fetal lung during the 2nd trimester of gestation. To determine the presence of β receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity β antagonist,I25I-iodocyanopindolol, in membrane particulates from the lungs of 2nd trimester abortuses (15-23 wk). Binding of125I-iodocyanopindolol was saturable and of high affinity (dissociation constant=40 pM). Binding was stereo selective as determined by competition studies with (—) and (+) stereoisomers of propranolol. Agonist affinities (isoproterenol > epinephrine » norepinephrine) were consistent with a predominance of 0-2 receptors; this predominance was confirmed by competition studies with the specific β-2 receptor antagonist ICI118-551 (75% 0-2, 25% 0-1). The concentration of β-adrenergic receptors increased with gestational age. To assess the functional coupling of the β receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with β agonists and determined the amount of cAMP generated. β Agonists stimulated cAMP generation more than 2-fold. We conclude that β- adrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

High levels of plasma erythropoiesis stimulating factor(s) (ESF) have been found in neonatal WLOmice during rapid growth. A previous study on hypertransfused neonatal animals indicated that the high ESF could not be due to the concomitant postnatal anemia alone. The present investigation was performed to answer the question: Is the high plasma ESF in neonatal WLO-mice erythropoietin (Ep) alone, or Ep in combination with other factors? The ESF of plasma from 20-day-old animals and standard Ep were compared in a cell culture assay for ESF based on erythroid colony formation, and also by means of gel filtration chromatography and affinity chromatography. Nonfractionated plasma and standard Ep showed parallel dose response curves and additive activity in the ESF assay. After gel filtration the detectable ESF of plasma was eluted in the same position as that of standard Ep, corresponding to an estimated molecular weight range of 34-65000 daltons. The ESF of intact plasma, fractionated plasma, and standard Ep were identically bound to and eluted from the affinity chromatography column. These results show that the ESF of plasma from 20-day-old animals can neither be separated into several factors, nor distinguished from that of standard Ep by the methods used. It is therefore concluded that the high plasma ESF found in neonatal WLOmice probably consists of Ep alone.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The purpose of this study was to compare the pharmacological characteristics and actomyosin content of arterial and venous tissue at different times during development. Rings of arteries (femoral, renal, carotid, pulmonary) and veins (saphenous, pulmonary, jugular) were obtained from 1 wk, 1 month, and adult dogs, mounted at their optimal length for force development and the contractile response to potassium chloride and phenylephrine determined. The strain at optimal length was less at all ages in pulmonary artery and pulmonary and jugular veins than in other vessels. All vessels exhibited an increase in maximum contractile response with development but the increase was greater for phenylephrine. In general, the magnitude of the maximum response of the jugular and pulmonary veins and pulmonary artery was less than other vessels at all ages. The sensitivity (half maximum response) either increased or was unchanged in arteries with development, while in the veins it either decreased or was unchanged. The relaxant effects of verapamil and isoproterenol were determined on potassium chloride contracted vessels. Arterial tissue was minimally responsive to isoproterenol at all ages while venous tissue either increased its responsiveness (saphenous, pulmonary) with development or remained highly responsive (jugular). Verapamil, unlike isoproterenol, was an effective relaxant of all vessels. The actomyosin content (mg/mm) of femoral and renal arteries and saphenous and jugular veins increased with development but this increase was accompanied by a parallel increase in total protein so that the ratio (actomyosin/total protein) was unchanged. In jugular veins from adult dogs this ratio was smaller than in arterial tissue. In general, it can be concluded that arterial and venous tissues increase their maximum contractile response during maturation. Because the maximum response to agents with different mechanisms of action (potassium chloride, phenylephrine) increased at different rates, the increase must be due to more than a quantitative increase in contractile material, possibly to differences in the rate of maturation of their respective excitation-contraction coupling processes. However, when maturational changes in other characteristics are compared, differences are observed between arteries and veins as well as between vessels within a given class indicating intervessel heterogeneity in maturation.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

ABSTRACT.Marked leukopenia and sequestration of granulocytes in the lung are consistently seen in serve early onset group B streptococcal (GBS) disease in human infants. To investigate the role of granulocytes as potential mediators in the pulmonary pathophysiology of this disease, the effects of intracenously adminstered GBS type III toxin were studied in young lambs before and after granulocyte depletion with hydroxyurea. Granulocyte depletion markedly reduced the 4-fold increase in total lung resistance and the decrease in dynamic compliance observed after GBS toxin. Granulocyte depletion significantluy attenuated the pulmonary hypertension, hypoxema and increased minute ventilation present during the first phase of the response (0.5-1 h after GBS toxin). It did not significantly alter the increase in lung lymph flow and protein clearance during the second phase of the response (3.5-5 h after GBS toxin). The result indicates that granulocytes are involved as, mediators of the changes in lung mechanics seen after GBS toxin infusion in young lambs. Granulocytes contribute to the pulmonary hypertension and decrease in arterial oxygenation, but other mediators appear to be responsible for the injury of the vascular endothelium.

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID