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Biomedical subjects

A Jobe

Publications and source records attributed to A Jobe.

At least 37 records · Page 2Linked to original sources
PubMed1991

Size selectivity of lung protein accumulation in preterm ventilated lambs.

The 1-hour net accumulation of four labeled proteins of different sizes (6.5, 29, 69 and 150 kD) from the vascular space into the lungs and airspaces was measured in preterm ventilated lambs at 132 days gestational age. Lambs treated with Survanta, a surfactant prepared from bovine lung, were studied at 1, 3, 5 and 8 h after birth, while lambs not treated with this surfactant were studied up to 5 h of age because of severe respiratory failure. The labeled proteins were lost from the vascular space more rapidly over the first 1 h of life than at later times (p less than 0.01). Labeled protein recoveries were similar at 1 and 3 h in surfactant and control lambs and decreased by 8 h in surfactant-treated lambs (p less than 0.05). In both the surfactant-treated and control animals, there was a sequential decrease in labeled protein recoveries based on protein size (p less than 0.01). There was no change with time in size selectivity for accumulation of the labeled proteins into the lungs for either the control or surfactant-treated lambs, although surfactant treatments decreased accumulation of the 6.5 and 29 kD proteins at 5 h when compared to the control group (p less than 0.05). Labeled protein recoveries in alveolar washes demonstrated less size selectivity. These studies documented that size selectivity of the vascular endothelium did not change over the first 8 h of life in preterm ventilated lambs, a pattern that was not indicative of progressive lung injury.

Animals↗
PubMed1990

Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Animals↗
PubMed1989

Metabolism of intratracheally administered unsaturated phosphatidylcholines in adult rabbits.

Twenty-five adult rabbits were each injected intratracheally with a solution containing 1-palmitoyl-2-[3H]palmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-[14C]oleoyl-PC that had been associated with with 32P-labeled natural rabbit surfactant. The animals were killed in groups of 5 at 1, 4, 8, 15 and 24 h after isotope injection. Isotope recovery and PC specific activities were measured in alveolar washes, lung homogenates, lamellar bodies and microsomes. The percent clearance per h of PC was very similar for the three labels and were; 3.56, 3.44 and 3.00%, respectively, for the 3H-, 14C- and 32P-labeled PC in the total lung (alveolar wash plus lung homogenate) and 3.84, 3.79 and 3.70%, respectively, for alveolar wash alone. The intracellular pathways of the three labels were assessed by comparing the specific activities in the lamellar bodies over 24 h as well as comparing the ratios of lamellar body to microsome specific activities over this period. These ratios were very similar for the monoenoic and saturated PC labels over time, indicating comparable recycling. In a separate experiment, three other unsaturated species; 1,2-[14C]dioleoyl-PC, 1-palmitoyl-2-[14C]linoleoyl-PC, and 1-palmitoyl-2-[14C]arachidonyl-PC were compared to 1-palmitoyl-2-[14C]oleoyl-PC. Recovery in the alveolar wash and total lung were similar at 16 h for all four labeled phospholipids. The intracellular pathways were also similar, except for the arachidonyl compound. More relative to the lamellar bodies as compared to the other. Thus, the catabolic pathways were similar for the saturated and unsaturated PC species initially present in the airspaces. The only metabolic difference between the compounds appears to be in the intracellular handling of the arachidonic species.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Lung perfusion and aerosol distributions in preterm ventilated lambs.

The relative distributions of ventilation as measured by 99Tc-sulfur colloid aerosol deposition and pulmonary perfusion (measured with radiolabeled microspheres) were determined in 12 preterm lambs that were delivered at 138 days gestational age and ventilated for 4 hrs. To verify that unventilated lung segments in these lambs would have decreased perfusion, a balloon catheter was placed in a major bronchus either at birth or after 2 hrs of ventilation. This catheter prevented ventilation of 24.5 +/- 3.2% of the lung tissue. After 4 hrs of ventilation, the lambs were sacrificed and the lungs were divided into about 60 1-g pieces. Apart from the occluded, atelectatic segments, the lungs were visually well aerated with only 5.3 +/- 1.8% of the nonobstructed lungs being spontaneously atelectatic. There was a 66.5 +/- 0.07% decrease in blood flow to the area of lung made atelectatic by the balloon. The blood flow also was decreased to lung regions assessed to be spontaneously atelectatic. No 99Tc-sulfur colloid was recovered from balloon-occluded lung regions, and less 99Tc-sulfur colloid was found in the spontaneously atelectatic areas than in aerated lung regions. There were significant correlations (P less than 0.001) between pulmonary blood flow and aerosol recovery in each of the 12 animals. Premature lambs had a wide variability in ventilation and perfusion, but the relative ventilation to perfusion ratio was regulated to minimize the intrapulmonary shunt.

Aerosols↗
PubMed1989

Surfactant metabolism in surfactant-treated preterm ventilated lambs.

Preterm lambs were delivered at 132 days gestational age, treated with 100 mg/kg radiolabeled natural sheep surfactant or Surfactant TA, and ventilated for times up to 24 h. Compared with an untreated group that developed respiratory failure by 5 h, both surfactant-treated groups had stable respiratory function to 24 h. Although only approximately 13% of the labeled surfactant phosphatidylcholine was recovered by alveolar wash at 24 h, there was no significant loss of the labeled phosphatidylcholine from the lungs. Labeled palmitic acid intravascularly injected at 1 h of age comparably labeled lung phosphatidylcholine in the three groups of lambs at 5 h; however, only approximately 0.5% of the labeled phosphatidylcholine was secreted to the air spaces of surfactant-treated lambs at 24 h. Labeled lysophosphatidylcholine given with the natural sheep surfactant was taken up by the lungs, converted to phosphatidylcholine with 30-40% efficiency, and resecreted to the air spaces, demonstrating recycling of a phospholipid. The large surfactant aggregates recovered from alveolar washes by centrifugation were surface active and contained approximately 76% of the air-space phosphatidylcholine in both surfactant-treated groups. Although clinical status was comparable, alveolar washes and surfactant subfractions from Surfactant TA-treated lambs had better surface properties than did sheep surfactant-treated lambs. These studies identified no detrimental effects of surfactant treatments on endogenous surfactant metabolism and indicated that the surfactants used for treatments were recycled by the preterm ventilated lamb lung.

Animals↗
PubMed1989

Clearance of phosphatidylcholine and cholesterol from liposomes, liposomes loaded with metaproterenol, and rabbit surfactant from adult rabbit lungs.

Rabbits were given by tracheal instillation liposomes, liposomes carrying metaproterenol sulfate (MPS) and suspended in a MPS solution, rabbit surfactant, or rabbit surfactant suspended in a MPS solution. The lipid suspensions were labeled with [14C]cholesterol and [3H]phosphatidylcholine. The percent recoveries of the labels were measured over 24 h in alveolar wash, lung tissue after alveolar wash, and the total lungs. All clearance curves for both phosphatidylcholine and cholesterol from liposomes were the same in the presence or absence of MPS. Alveolar clearance curves for both labels from rabbit surfactant were the same; however, the surfactant-associated labels were cleared to the lung tissue more rapidly than were the liposome-derived labels. Despite different alveolar clearance curves, all clearance curves for cholesterol from the total lungs were similar at a rate of 20 to 30%/24 h of the injected labeled cholesterol. Phosphatidylcholine was cleared from the total lungs more rapidly, at rates from 35 to 56%/24 h. Although MPS did not change labeled liposomal lipid clearance, the beta-agonist increased surfactant lipid clearance. The different responses to beta-agonist and the different alveolar clearance curves indicated distinct alveolar-to-lung tissue metabolism for liposomal versus surfactant phosphatidylcholine and cholesterol, although overall lung clearance rates were similar.

Animals↗
PubMed1989

Vascular to alveolar leak of iron dextran (120 kD) in the immature ventilated rabbit lung.

Rabbit fetuses were delivered by hysterotomy on day 27 or 28 of gestation. Immediately after birth, the animals were tracheotomized and received by intravenous injection 0.2 mu Ci radiolabeled albumin and 11 mg iron dextran in 0.2 ml saline. The newborn rabbits then were ventilated artificially with a tidal vol of 12 ml/kg for 5-20 min. One group of nonventilated animals served as controls. At the end of the experiment, one lung was lavaged via the airways and the other was fixed for histologic examination. The recovery of labeled albumin and iron dextran in the lavage fluid was quantified. Iron dextran complexes were easily identified in the lung sections by staining with Prussian blue. Iron dextran accumulated in the airspaces of animals delivered on day 27 (about 4% of the injected dose during 10-20 min of ventilation). The albumin leakage was slightly higher than that of the dextran, a result consistent with different mol wt of the markers. The vol density of leaking alveoli in histologic sections increased with time, from 0 at birth to a mean value of 0.36 after 20 min of ventilation. The leakage starts as a focal event, gradually involving more and more terminal airspaces. In the histologic sections, there was no indication of a significant leakage at the bronchiolar level, although the epithelium of terminal and preterminal airways was clearly injured in all ventilated animals.

Albumins↗
PubMed1989

Effect of maternal hormone treatment on lung protein leakage and lung function of preterm newborn rabbits.

We tested whether maternal administration of corticosteroids, thyrotropin-releasing hormone (TRH), triiodothyronine (T3) or their combinations, would improve lung function of ventilated preterm newborn rabbits. Maternal corticosteroids and T3 treatments did not improve lung compliance; TRH did. The major effect observed was a large improvement in lung compliance following maternal treatment with corticosteroids plus TRH in animals treated with surfactant. These agents made the lung "receptive" to the surfactant treatment. T3 did not improve lung function and no augmented response to surfactant was seen. None of the treated groups had surfactant pool sizes significantly different from controls. The mechanisms of action of corticosteroids and/or TRH seemed to be independent of changes in surfactant pool sizes.

Adrenal Cortex Hormones↗
PubMed1989

In vivo clearance of natural and modified surfactant.

The loss of radiolabelled phosphatidylcholine associated with surfactants and lipid extracts of surfactants from different species sources was measured following tracheal injection into the lungs of adult and 3 day old rabbits. Clearance was more rapid from the lungs of adult than 3 day old rabbits. The percent labelled phosphatidylcholine cleared per 24 h did not change independently of dose injected indicating that clearance and catabolic pathways were not saturable in either group of rabbits. Different species sources or lipid extraction of natural surfactants did not alter clearance rates very much in the 3 day old rabbits. Small differences in clearance rates were identified by comparing rabbit surfactant with calf surfactant or Surfactant-TA in the adult rabbits. These results indicate that the lungs of developing and adult rabbits can clear large doses of surfactants from multiple sources at rates comparable to the species common natural surfactant.

Animals↗
PubMed1989

Protein leaks and surfactant dysfunction in the pathogenesis of respiratory distress syndrome.

This article reviews the phenomenon of surfactant inactivation by soluble proteins. Following surfactant treatment of preterm lambs, the initial clinical response was not maintained. The surface tensions that were low in the lungs following surfactant treatment increased to high values concurrently with the return of severe respiratory failure. The surface properties of the surfactant that remained in the airways and alveoli could be restored if the soluble proteins were removed. These soluble proteins inactivated different surfactants to different degrees and the interaction was very concentration dependent. The proteins entered the lungs of the preterm lamb because of the tendency of these lungs to form pulmonary oedema. Similar surfactant inactivation occurred in the lungs of infants with respiratory distress syndrome. A variety of manipulations influenced the formation of proteinaceous pulmonary oedema, suggesting that new therapeutic strategies could be developed to treat infants with RDS.

Humans↗
PubMed1988

Clearance of surfactant phosphatidylcholine from adult rabbit lungs.

Rabbits were given various doses of rabbit surfactant and treatment doses of approximately 100 mg/kg body wt of calf surfactant and Surfactant TA by tracheal injection. The linear loss of radiolabeled phosphatidylcholine from the total lung (alveolar wash and lung tissue) was 3.1, 1.5, and 1.8%/h for rabbit surfactant, calf surfactant, and Surfactant TA, respectively. After 24 h only 6% rabbit, 19% calf, and 9.7% Surfactant TA phosphatidylcholine were recovered by alveolar wash, and alveolar macrophage fractions contained less than 1% of the injected labeled phosphatidylcholine. The loss of rabbit surfactant phosphatidylcholine 24 h after tracheal injection did not change for doses in the range of 0.5-70 mumol phosphatidylcholine per kilogram, indicating nonsaturable clearance pathways. Very little of the labeled rabbit surfactant phosphatidylcholine lost from the lungs could be recovered in other organs, and 90% of the recovered labeled phosphatidylcholine in the liver was unsaturated, implying de novo synthesis using precursors from degraded phosphatidylcholine. The surfactant did not change endogenous lung phosphatidylcholine synthesis or its secretion to the alveolus. There were no adverse effects of the surfactant treatments noted in healthy rabbits.

Animals↗
PubMed1988

Corticosteroid potentiation of surfactant dose response in preterm rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 days gestational age. Both corticosteroid-treated and control animals then received exogenous natural rabbit surfactant at birth at doses of 0-75 mg lipid/kg. After 10 min of ventilation at tidal volumes of 12-15 ml/kg, static pressure-volume measurements were made. At all surfactant doses there was a significantly higher maximal lung volume, higher dynamic compliance, and lower pressure requirement in the corticosteroid-treated than in the control rabbits (P less than 0.01). Control animals showed incremental improvements in dynamic compliances and maximal lung volumes up to a dose of 50 mg/kg, whereas corticosteroid treated animals improved to a maximum at the low dose of 15 mg/kg (P less than 0.01). However, surface tension as assessed by lung stability index improved with increasing surfactant dose but was not significantly different between corticosteroid-treated and control animals at a given dose. The results imply that maternal corticosteroid treatment potentiates surfactant replacement by a change in lung structure that is independent of surface tension effects.

Animals↗
PubMed1988

Pulmonary effects of acute prenatal asphyxia in ventilated premature lambs.

The effect of profound repetitive prenatal asphyxial insults on the cardiopulmonary function of premature ventilated lambs was studied. Twenty-nine fetal lambs (approximately 138 days gestational age) were exteriorized. In 16 of these lambs, the umbilical cord was occluded for 4 min then released for 10 min. This asphyxial episode was repeated until the arterial pH was approximately 7.00, and the mean arterial blood pressure was less than 40 mmHg and falling. The 13 control lambs were simply exteriorized with the umbilical circulation intact. The lambs were then ventilated for 3-4 h. There were no differences between the control vs. asphyxiated lambs in pulmonary compliances (0.57 and 0.58 ml.cmH2O-1.kg-1) wet-to-dry weight ratios (8.18 and 7.55), cardiac outputs (177.8 and 141.8 ml.kg-1.min-1), surfactant-saturated phosphatidylcholine pool sizes, or atrial and/or ductal shunts. Asphyxia did not interfere with the redirection of blood away from atelectatic lung segments created by bronchial obstruction with balloon catheters. Also, although the bidirectional flux of protein into and out of the airways of these preterm lambs was large relative to term lambs, there was no effect of asphyxia on this protein leak. In this animal model, prenatal asphyxia did not impact negatively on the severity of the respiratory failure.

Animals↗
PubMed1988

Clearance of surfactant phosphatidylcholine via the upper airways in rabbits.

A possible route of clearance of surfactant phosphatidylcholine from the lungs is via the airways. To quantify surfactant loss via this pathway, latex bags were surgically placed into the abdomens of adult rabbits such that secretions cleared via the esophagus could be collected. The rabbits then were given treatment or trace doses of radiolabeled phosphatidylcholine-surfactant by tracheal injection and/or intravascular radiolabeled precursors of phosphatidylcholine. Labeled saturated phosphatidylcholine was measured in all fluids that were collected from the bags at 2-h intervals for 24 h and in alveolar washes and lung tissues at 24 h. No more than 7% of either treatment or trace doses of intratracheal surfactant-saturated phosphatidylcholine was lost via clearance up the airways over 24 h. Clearances of endogenously synthesized and secreted saturated phosphatidylcholine were estimated to be no more than 3% of the flux of labeled saturated phosphatidylcholine through the alveolar pool. These experiments demonstrate that surfactant phosphatidylcholine clearance via movement up the airways is not a major pathway leading to surfactant catabolism.

Animals↗
PubMed1988

Clearance of treatment doses of surfactant. Effect of lipid extraction and aggregate sizes.

Three-day-old rabbits were given intratracheal injections with a variety of surfactants at doses of about 100 mg lipid/kg, doses commonly used in clinical trials of surfactant for respiratory distress syndrome. Calf and sheep natural surfactants isolated by centrifugation of alveolar washes were compared with Surfactant-TA and two aggregate sizes of lipid solvent extracted sheep surfactant by measuring the percent recoveries of labeled phosphatidylcholine in alveolar washes and lung tissue at times to 48 h after surfactant injection. Surfactant-TA and the lipid extracted surfactants did not contain the 28 to 35-kdalton surfactant protein. All surfactants had similar linear clearance rates from the total lung (alveolar wash plus lung tissue), independent of species source, extraction with lipid solvents, or aggregate sizes of the phospholipids in suspension. There were no metabolic consequences to lipid extraction, the loss of 28-35 kdaltons of protein, or changes in aggregate sizes of surfactant lipids when injected in treatment doses into the airways of 3-day-old rabbits.

Animals↗
PubMed1988

Maternal treatments with corticosteroids and/or T3 change lung volumes and rupture pressures in preterm rabbits.

Pregnant does were treated with betamethasone, T3, the combination of beta-methasone and T3 or vehicle control on days 24 and 25 of gestation. At 26 days gestational age, pressure-volume curves and lung rupture pressures and volumes were measured in the various groups of rabbits randomized to receive saline or surfactant by tracheal injection. Alveolar wash and lung tissue quantities of saturated phosphatidylcholine were comparable across the hormone-treated and control groups. Corticosteroids increased maximal lung volumes more than did T3. Corticosteroids augmented the lung volumes of surfactant-treated lungs more than did T3, and no additive effects on lungs treated with both hormones and surfactant were noted. Both corticosteroids and surfactant decreased lung rupture pressures from 51.7 +/- 4.1 to about 44 cm H2O. T3 decreased lung rupture pressure to 48.9 +/- 3.9 cm H2O and the combination of T3 and corticosteroids resulted in rupture pressures comparable to T3 alone. There were no additive effects of the combined use of T3 and corticosteroids and T3 antagonized the decreased lung rupture pressures caused by corticosteroids. While T3 did not alter the increase in lung volumes noted with corticosteroids, lung structure as assessed by lung rupture was differentially affected by the two hormones.

Animals↗
PubMed1988

The role of surfactant in neonatal adaptation.

The fetal lung has complex mechanisms for surfactant accumulation and secretion that prepare the fetus for an uncomplicated transition to air breathing. Recent experiments indicate that this transition is not just a process of secretion of accumulated stores, but involves dynamic processes of mobilization of intracellular pools, alveolar surfactant reuptake, and complex changes in alveolar surfactant fractions. The intricacies of these processes and the relative importance of the various proposed secretagogues remain to be further explored. Surfactant is necessary, but not sufficient for normal neonatal pulmonary adaptation. Without adequate central respiratory drive, respiratory muscles, and lung structural maturation, normal respiratory adaptation will not occur.

Adaptation, Physiological↗