Biomedical subjects

A Jobe

Publications and source records attributed to A Jobe.

At least 19 recordsLinked to original sources

PubMed1992

Effects of antenatal thyrotropin-releasing hormone, antenatal corticosteroids, and postnatal ventilation on surfactant mobilization in premature rabbits.

OBJECTIVE: The effects of antenatal hormones on postnatal surfactant mobilization were evaluated in preterm rabbits. STUDY DESIGN: Pregnant rabbits were treated with vehicle, betamethasone, or thyrotropin-releasing hormone for 2 days before cesarean section at 29 days' gestation (term 31 days). Newborns were mechanically ventilated or allowed to spontaneously breathe, and groups were compared by analysis of variance. RESULTS: Neither antenatal corticosteroids nor thyrotropin-releasing hormone increased radiolabeled precursor incorporation, alveolar wash or total lung saturated phosphatidylcholine pools, lung clearance of radiolabeled rabbit surfactant, or estimated net secretion of saturated phosphatidylcholine. However, saturated phosphatidylcholine pools in alveolar wash increased 2.7-fold during the first 24 hours in spontaneously breathing rabbits versus 2.1-fold in mechanically ventilated thyrotropin-releasing hormone-treated and control rabbits (p less than 0.05). In addition, estimated net secretion of precursor-derived saturated phosphatidylcholine was 50% higher after 24 hours in spontaneously breathing rabbits. CONCLUSION: Mechanical ventilation may have hindered the mobilization of surfactant saturated phosphatidylcholine pools to the alveolar space after birth in preterm rabbits, but maternal hormonal therapies did not appear to influence this adaptive process or change surfactant metabolism.

Adrenal Cortex Hormones↗

PubMed1992

Antenatal ambroxol effects on surfactant pool size and postnatal lung function in preterm ventilated rabbits.

Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool sizes were measured. One half of the ambroxol treated and control rabbits were given surfactant at delivery. Although surfactant improved lung function comparably for control and ambroxol treated rabbits, ambroxol treatments did not change ventilatory pressure requirements, compliances, or the recovery of intravascular labeled albumin in the lungs. Ambroxol treatments tended to increase lung volumes as evaluated by pressure-volume curves. The ambroxol treatments significantly increased lung tissue SatPC by 22%, but there were no changes in alveolar SatPC pool values. These results do not indicate a large effect of ambroxol on lung function in preterm rabbits.

Ambroxol↗

PubMed1991

Leakage of macromolecules in ventilated and unventilated segments of preterm lamb lungs.

The movement of macromolecules into and out of unventilated lung segments was evaluated in prematurely delivered and ventilated lambs. Seven lambs at 130 days gestational age had a bronchial balloon placed at birth before the first breath to obstruct the left lower lobe. Surfactant and 131I-albumin were instilled into the left lower lobe while surfactant and 125I-albumin were instilled into the remaining lung, and 70,000 molecular weight [3H]dextran was given into the vascular space at birth. Twenty-five percent of the lung by weight was not ventilated, and 24% of the total leak of dextran from the vascular space was recovered in the unventilated lungs at 3 h. An epithelial leak of protein from the two lung regions was documented by the loss of 11.4 and 18.4% of the labeled albumins in the nonventilated and ventilated lung regions, the appearance of 4.9 and 7.5% of the airway-instilled albumin in the vascular space from the nonventilated and ventilated lung regions, and the recovery of the labeled albumins in the carcasses of the lambs. The bidirectional flux of macromolecules was larger in the ventilated than in the nonventilated lung regions, indicating that ventilation can increase the leak of protein in the preterm lung. The lung areas that were never exposed to ventilation or oxygen also demonstrated a large bidirectional flux of macromolecules, a finding not present in the fetus, fullterm newborn, or adult. These findings indicate that ventilation is not solely responsible for the increased protein leak found in preterm lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

PubMed1991

Corticosteroid and thyrotropin-releasing hormone effects on preterm sheep lung function.

Four groups of twin sheep fetuses were catheterized at 121 days of gestational age and intravenously infused with saline, 0.75 mg.kg-1.h-1 cortisol for 60 h, five intermittent bolus injections of 5 micrograms/kg thyrotropin-releasing hormone (TRH) at 12-h intervals, or both hormones before delivery at 128 days. At birth, the lambs were randomized to receive surfactant or no treatment. Surfactant treatment improved lung function of all the groups. Corticosteroids alone and in combination with TRH improved compliance and gas exchange as well as pressure-volume curves. Corticosteroids alone dramatically decreased the recovery of intravenously administered radiolabeled albumin in the lung tissue and air space and improved the pulmonary response to surfactant treatment. There were no additional effects of TRH when given with corticosteroids on lung function or albumin leak. There were no changes in alveolar surfactant-saturated phosphatidylcholine pool sizes after any hormone treatment. The single significant effect of combined corticosteroid and TRH treatment was a fivefold increase in surfactant protein A in alveolar lavage fluid relative to all other groups.

Animals↗

PubMed1991

Nebulized vs. instilled exogenous surfactant in an adult lung injury model.

Three days after subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) to induce lung injury, adult rabbits were mechanically ventilated and lung function was evaluated. Each animal then received either nebulized Survanta (Neb Surv), nebulized saline (Neb Saline), nebulized gas alone (Neb Gas), or tracheally instilled Survanta (Inst Surv). The ventilation efficiency index (VEI) value increased significantly compared with pretreatment values (P less than 0.01) over a 3-h treatment period for the Neb Surv animals, whereas VEI values for the other three groups decreased after treatment (P less than 0.05). Arterial PO2-to-fraction of inspired O2 ratios and dynamic compliance values significantly decreased after treatment for the Inst Surv group (P less than 0.05). Pressure-volume curves demonstrated a significantly greater volume at maximal pressure for the Neb Surv group compared with each of the other groups studied (P less than 0.01). The calculated quantity of surfactant recovered in lung tissue for the Neb Surv group was only 4.9 +/- 1.0 mg lipid/kg compared with 100 mg lipid/kg delivered to the Inst Surv group. Surfactant administered as an aerosol resulted in modest physiological improvements in this model of lung injury and was superior to the tracheal instillation technique.

Aerosols↗

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↗