Various doses (0-4.8 mg) of porcine surfactant were administered into the airways of immature newborn rabbits delivered at a gestational age of 26 days and 17-23 h. When the estimated concentration of exogenous surfactant in the lung liquid was less than or equal to 0.75 mg/ml (dose 0.6 mg), an average tidal volume of no more than a 3.0 ml/kg was obtained by mechanical ventilation with a peak insufflation pressure of 25 cm H2O, but when the estimated concentration was increased to 1.5 mg/ml (dose 1.2 mg), an average tidal volume of 17.7 ml/kg was attained, and the survival rate during a 30-min period of artificial ventilation improved significantly, from 14% to 53%. Even larger average tidal volumes, about 25 ml/kg, were recorded in animals with estimated surfactant concentrations of 3 and 6 mg/ml (doses 2.4 and 4.8 mg, respectively). In vitro observations revealed that the surface adsorption time of the surfactant suspension decreased non-linearly from 20 to 1 sec when the concentration was increased from 1 to 3 mg/ml. The minimum surface tension during cyclic film compression also decreased non-linearly from greater than 15 to less than 3 mN/m with the same increments in concentration. This led us to conclude that, under the present experimental conditions, the critical concentration of surfactant in fetal lung liquid at birth (about 3 mg/ml) is close to the concentration required in vitro for rapid adsorption and optimal dynamic surface properties.

Administration, Oral↗

PubMedDate not supplied

Effect of amiloride and surfactant on lung liquid clearance in newborn rabbits.

Immature and nearly mature fetal rabbits (gestational age 27.5 and 29.5 days, respectively) were obtained by hysterotomy and tracheotomized at birth. Immature rabbits received, via the tracheal cannula, 2.5 ml/kg of either normal saline, porcine surfactant (60 mg/ml), 1 mM amiloride in normal saline, or a mixture of surfactant and amiloride; nearly mature rabbits received either normal saline, or 1 mM amiloride in saline. The neonates were ventilated with a tidal volume of approximately 10 ml/kg for 0-60 min (immature animals) or 0-120 min (nearly mature animals). The lungs were then excised for determination of wet lung weight/body weight ratio (LW/BW). The right lung was further processed for quantification of extravascular lung water (EVLW) per unit dry lung weight, and the left lung fixed for measuring the size of perivascular 'cuffs' (adventitial tissue including lymphatics) in histological sections, using vascular lumen as reference volume. Immature animals receiving surfactant had improved compliance and smaller perivascular cuffs in comparison with the other groups. In immature animals amiloride had no effect on compliance, LW/BW, and EVLW, but reduced perivascular cuff size at 15 min. Nearly mature animals receiving amiloride had higher values for LW/BW and EVLW at 120 min, and lower perivascular cuff size at 15, 60, and 120 min, in comparison with saline-treated litter-mates. We conclude that surfactant improves lung-thorax compliance and reduces perivascular fluid accumulation in immature newborn animals without influencing total lung water content, and that amiloride retards fetal lung liquid resorption in nearly mature newborn animals without affecting lung-thorax compliance during artificial ventilation.

Absorption↗

PubMedDate not supplied

Proliferation patterns of dorsal root ganglion neurons of cutaneous, muscle and visceral nerves in the rat.

In a previous study we provided evidence that dorsal root ganglion (DRG) neurons of different phenotypes have different birthdates. The present study aimed at determining if birthdates of DRG neurons are related to different types of peripheral nerves, namely cutaneous versus muscle, and somatic versus visceral. Pregnant rats were injected intraperitoneally with bromodeoxyuridine (BrdU) to label the neurons on one of the embryonic days E12-E16. When the progeny rats reached adulthood, a mixture of 1% B-fragment of cholera toxin and 1% isolectin B4 from Griffonia simplicifolia I was injected into the peripheral nerves, or a 5% Fluoro-Gold solution was applied to the transected end of the nerves. The saphenous and sural nerves were used as cutaneous nerves, the gastrocnemius nerve as a muscle nerve, the intercostal nerves T9-11 as somatic nerves and the greater splanchnic nerve as a visceral nerve. Cell size measurements were made of DRG neurons labeled from the two cutaneous nerves and the muscle nerve, as well as of neurons of the saphenous and gastrocnemius nerves labeled by BrdU at different embryonic stages. Most of the DRG neurons of the muscle and intercostal nerves were generated early, with peaks at E13, and those of the cutaneous and visceral afferent nerves later, with peaks at E14. The temporal differences were reflected in the cell size spectrum, the muscle nerve having a greater proportion of large neurons compared to the cutaneous nerves. The findings add to previous knowledge regarding the sequence of development of different DRG phenotypes.

Age Factors↗

PubMedDate not supplied

Shelf-life of bank blood and stored plasma with special reference to coagulation factors.

Whole blood and plasma drawn into plastic bags containing citrate-phosphate-dextrose (CPD) and stored at 4 degrees C for various periods were studied for variations of coagulation factor and fibrinolytic activity. The blood was collected and processed in the conventional way. The most labile component, factor VIII coagulant activity, decreased to about 50 percent of its original value within the first 24 hours in whole blood, but thereafter, it decreased more slowly. Storage of whole blood for 6 hours at 4 degrees C had an insignificant effect on VIII coagulant activity; an even slower decrease was found for factor VIII coagulant antigen. The major fall in VIII coagulant activity occurred between 6 and 24 hours of whole blood storage. Factor VIII-related antigen remained normal for about 1 week, but on further storage showed signs of proteolytic degradation. In plasma, there was a successive decrease in VIII coagulant activity with its minimum level (about 50% decrease as compared with the original level) after 7 to 14 days of storage. All other factor VIII activities in plasma remained unchanged throughout the study. Factor V retained its activity for about 1 week in the whole blood. Factors II, VII, IX, X, XII, XIII and fibrinogen did not fall below normal during a storage period of 35 days, nor was there any indication of increased fibrinolytic activity in either whole blood or plasma. Storage of whole blood and plasma at 4 degrees C for 1 to 2 weeks seems to have relatively little effect on the levels and function of various coagulation components with the possible exception of factor VIII coagulant activity.

Antigens↗

PubMedDate not supplied

New avenues in surfactant research.

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Forecasting↗

PubMedDate not supplied

Artificial surfactants based on analogues of SP-B and SP-C.

The hydrophobic proteins SP-B and SP-C are important components of natural surfactant preparations currently used in clinical practice, and physiologically active surfactants can be made from isolated SP-B and/or SP-C reconstituted with synthetic lipids. Efforts have been made to produce these polypeptides, or analogues with similarfunction, by organic synthesis or expression in heterologous systems. It is important to obtain proper folding of the synthetic peptides, as required for optimal interaction with the surfactant lipids. Another issue is to avoid loss of SP-C activity due to alpha-helix to beta-sheet transition. This latter problem can be circumvented by replacing the polyvaline stretch of SP-C with a polyleucine stretch containing a few lysines. Palmitoylation of cysteines or serines at positions 5 and 6 also seems important for the properties of SP-C. SP-B, which is too big a molecule to be easily produced by organic synthesis. apparently can be replaced in an artificial surfactant by a peptide capable of cross-linking phospholipid bilayers. The development of synthetic analogues of the surfacant proteins might make it possible to tailor artificial surfactants for specific therapeutic missions, for instance by enhancing resistance to inactivation by meconium, plasma proteins, or oxygen radicals or maximizing bacteriostatic effects.

Animals↗

PubMedDate not supplied

Longitudinal study of young children's responses to challenging achievement situations.

Three studies were conducted to replicate and extend Dweck's findings regarding young children's responses to challenging achievement situations. Dweck's dichotomous helplessness classification system (i.e., task choice, task choice reason) was replicated with kindergartners, n = 235 (50% male), and first graders, n = 70 (46% male). To test whether individual differences in young children's responses to challenging situations are stable over time, 1- and 5-year follow-ups of the kindergartners were conducted. On the basis of children's responses on age-appropriate behavioral tasks, a composite of cognitive, behavioral, and affective helplessness indices predicted helplessness at 1 and 5 years later, n = 114 (50% male), above and beyond kindergarten task ability and gender, p<.05. Kindergarten helplessness predicted teacher ratings of children's helplessness 5 years later as well, p<.05. The implications of these findings for early intervention are discussed.

Adaptation, Psychological↗

PubMedDate not supplied

Immunochemical and immunohistochemical evaluation of lung permeability in ventilated newborn rabbits.

These experiments were designed to quantify the vascular-to-alveolar leakage albumin in the neonatal lung and to analyze the distribution of leaking airspaces in the lung parenchyma. Immediately after delivery, newborn rabbits with gestational age 27-29 days received an intravenous injection of human albumin as a marker and were ventilated for 15 min with standardized tidal volume (10 ml/kg). After the period of ventilation the lungs were either lavaged via the airways or fixed for histological studies. The median amount of albumin in lung lavage fluid, determined by immunodiffusion, was 4.8% of the injected dose after 27 days, 1.3% after 28 days, and 0.4% after 29 days of gestation; it was inversely correlated with the compliance of the respiratory system (r = -0.78; p less than .001). Immunohistochemical examination of lung section revealed that the leak was not diffuse; even in animals with gestational age 27 days it involved only a median of 48% of total alveoli. The median amount of alveoli containing the label fell to 6% after 28 days and to 0% after 29 days gestation, correlating inversely with the compliance of the respiratory system (r = -0.53; p less than 0.01). We suggest that our experimental model is useful for histological demonstration of serum proteins leaking into the airpaces under experimental conditions and for evaluating the effect of therapeutic regiments on neonatal lung permeability.

Animals↗

PubMedDate not supplied

The origin in neonatal lung injury.

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Humans↗

PubMedDate not supplied

Radiologic observations in severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.

Ten newborn babies with severe respiratory distress syndrome, all dependent on artificial ventilation, were treated via the airways with the isolated phospholipid fraction of bovine or porcine surfactant. After treatment with surfactant at a median age of 10.5 h, there was in all patients a striking improvement of lung aeration in chest films, with a decrease in parenchymal fluid retention and in distension of bronchioli. These radiologic findings were associated with a dramatic improvement of oxygenation and a significant reduction of the right-to-left shunt. In spite of the rapid therapeutic response, four patients died from cerebral hemorrhage. One of the surviving patients developed bronchopulmonary dysplasia. Our findings document efficacy of this new surfactant preparation in the neonatal respiratory distress syndrome, but the long-term effects need to be further tested in randomized clinical trials.

Blood Gas Analysis↗