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Biomedical subjects

G Grossmann

Publications and source records attributed to G Grossmann.

At least 73 records · Page 4Linked to original sources
PubMed1988

Prolonged ventilation of the premature newborn rabbit after treatment with natural or apoprotein-based artificial surfactant.

Premature rabbit neonates (gestational age 27 days) were treated at birth with natural surfactant purified from chloroform extracts of porcine lung lipids either by acetone precipitation (Surfactant CK, n = 10) or liquid gel chromatography (Curosurf, n = 22). Another group of animals received artificial surfactant "reconstituted" from isolated low molecular weight (less than or equal to 15 K) apoproteins and synthetic dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) (Aposurf, n = 10). The phospholipid concentrations of the preparations were adjusted to provide the same individual dose of DPPC for each group of treated animals (3 or 4 mg). In comparison with untreated controls from the same litters, there was a 4-7-fold enhancement of lung-thorax compliance in all groups of surfactant-treated animals during a 3-h period of artificial ventilation. The average initial (20 min) compliance value was lower in the Aposurf-treated group than in animals receiving natural surfactant preparations, but the difference between the groups gradually diminished and was no longer statistically significant during the 2nd and 3rd h of artificial ventilation. Judged from the fall in tidal volume during ventilation with a short expiration phase (0.17 instead of 0.75 s), the apoprotein-based artificial surfactant was also less effective in stabilizing the lungs. A similar conclusion could be drawn from data on alveolar expansion in histological sections, evaluated by automated image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Respiratory failure in mice caused by a hybridoma making antibodies to the 15 kDa surfactant apoprotein.

Hybridoma cells were obtained by fusing spleen cells from mice, immunized against the 15 kDa porcine surfactant apoprotein, with a myeloma cell line. Adult mice were inoculated intraperitoneally with this hybridoma; mice that were not inoculated or were inoculated with myeloma cells served as controls. Lung-thorax compliance was measured at various intervals after inoculation. The animals were then killed for histologic-morphometric evaluation of alveolar air expansion, inflammatory reaction in the pulmonary parenchyma, and intraalveolar edema. In the hybridoma group, the mice developed respiratory failure 9 days after inoculation, with markedly reduced lung-thorax compliance, lung congestion, alveolar collapse, hemorrhagic pulmonary edema, and hyaline membranes. Morphometric data from the same animals showed reduced volume density of alveolar air, and increased volume densities of intraalveolar "fluid" (edema) and tissue components. These lung lesions are similar to those in the adult respiratory distress syndrome.

Animals↗
PubMed1988

Effects of antenatal hydrocortisone on tidal volumes in spontaneously breathing preterm newborn rabbits. Possible mediation by adrenal catecholamines.

Rabbit fetuses were injected on day 26 of gestation with hydrocortisone (2 mg) and delivered by hysterotomy 2 days later. The animals were tracheotomized at birth, and tidal volumes and esophageal pressures were recorded during spontaneous ventilation at standardized intervals from the first breath to the age of 2 h. In a subgroup of animals, the catecholamine content was measured in the adrenal glands. In comparison with littermate controls, tidal volumes were enlarged in hydrocortisone-treated neonates at the first breath and 60 min after birth; however, this effect was associated with an increased incidence of intra-alveolar hemorrhage. Hydrocortisone-treated animals also had a significantly increased adrenal content of adrenaline. Our data confirm a modest beneficial effect of antenatal hydrocortisone treatment on the fetal lung and suggest that this might in part be mediated by adrenal catecholamines. Stimulation of beta-adrenergic receptors could thus potentiate the effect induced by direct influence of glucocorticoids on fetal lung maturation.

Adrenal Glands↗
PubMed1987

Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.

Ten newborn infants (795-1680 g) with severe respiratory distress syndrome (RDS) were treated with the isolated phospholipid fraction of bovine or porcine surfactant, which was administered via the airways (dose 200 mg/kg), at a median age of 10.5 h. Before receiving surfactant, all the infants were on artificial ventilation (FiO2 0.6-1.0). Within 2 h after surfactant replacement, the arterial-to-alveolar PO2 ratio increased from 0.1 to 0.35. There was a concomitant improvement in lung aeration on the chest roentgenograms and a significant reduction in the right-to-left shunt. Four patients died of cerebral hemorrhage; two of them also had a patent ductus arteriosus. One surviving infant developed bronchopulmonary dysplasia, and another succumbed 8 months later to the sudden infant death syndrome. No antibodies against surfactant were detected in the sera of the survivors. Since our results show a significant improvement in lung function after replacement therapy, the efficacy of this new surfactant preparation should be further tested in randomized clinical trials.

Chromatography, Gel↗
PubMed1987

Automated image analysis of alveolar expansion patterns in immature newborn rabbits treated with natural or artificial surfactant.

Automated image analysis of histological lung sections was used to compare the efficacy of an artificial surfactant (dipalmitoylphosphatidylcholine + high-density lipoprotein, 10:1) and a natural surfactant (the phospholipid fraction of porcine surfactant, isolated by liquid-gel chromatography in ventilated immature newborn rabbits delivered after 27 days' gestation. Tidal volumes were significantly improved in each group treated with surfactant when compared with controls, but natural surfactant-treated rabbits had significantly higher tidal volumes than those receiving artificial surfactant. There were no statistically significant differences in alveolar expansion between the artificial surfactant group and the controls, but alveolar volume density and a shape factor (assessing the 'circularity' of terminal airspaces) were significantly higher in animals receiving natural surfactant. These animals also had a lower coefficient of variation of alveolar volume density and a lower alveolar average integral mean surface curvature, indicating a uniform pattern of alveoli with a smooth profile. We conclude that automated image analysis is useful for the quantitation of alveolar expansion patterns in immature neonatal lungs and that natural surfactant is superior to the artificial surfactant tested in the present study.

Animals↗
PubMed1986

Scanning electron microscopy of epithelial lesions induced by artificial ventilation of the immature neonatal lung; the prophylactic effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation were ventilated artificially for 5-10 min with a peak insufflation pressure of about 35 cm H2O, with or without previous treatment with natural surfactant via the airways. The alveolar expansion pattern and the surface structure of the airways were then examined by scanning and transmission electron microscopy. Animals not receiving surfactant had very irregular alveolar expansion and showed prominent desquamation of the bronchiolar epithelium with a strikingly ragged appearance of the mucosa in the scanning electron microscopic images. Litter mates treated with surfactant had improved alveolar expansion and a flattened but otherwise nearly intact bronchiolar epithelium. The findings confirm the beneficial effect of surfactant replacement on the immature neonatal lung.

Animals↗
PubMed1986

Effect of aminophylline on lung maturation in preterm rabbit fetuses.

Pregnant rabbit does were treated intravenously with aminophylline (6 mg/kg/day) from the twenty-fifth day after the day of mating, and the fetuses were delivered by hysterotomy on the twenty-eighth day. One group of neonates was breathing air, and another group 100% oxygen. Lung mechanics were evaluated in the newborn animals during spontaneous or artificial ventilation, and the lungs were studied histologically with particular reference to the alveolar volume density. In one series of experiments, the lungs were washed and the lavage fluid was analyzed for phosphatidylcholine and phosphatidylglycerol. Aminophylline-treated litters had greater body weights, an improved survival rate, and an increased amount of phosphatidylglycerol in lung lavage fluid. Respiratory frequency was increased in aminophylline-treated animals breathing air, but data on lung compliance showed no significant difference between treated and control animals. In the present model, the beneficial effect of aminophylline can be attributed largely to a combination of accelerated fetal growth and improved postnatal regulation of breathing and less to a specific influence on the biochemical and functional maturation of the lung.

Aminophylline↗
PubMed1986

Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage.

Severe respiratory insufficiency was induced in adult guinea pigs by repeated lung lavage. The animals were then ventilated for 75 min with 100% O2, insufflation pressure 28/6-8 cmH2O (2.7/0.6-0.8 kPa), frequency 30/min, and 33% inspiration time. One group of animals (I) was treated with protein-depleted porcine surfactant, prepared by a combination of sucrose-gradient centrifugation, heating to 90 degrees C, and chloroform/methanol extraction. Another group (II) received the phospholipid fraction of porcine surfactant, isolated from minced lungs by chloroform/methanol extraction and liquid-gel chromatography. Surfactant was administered in two 1-ml doses (lipid concentration 90 mg/ml) instilled via the tracheal cannula about 15 and 45 min after the lavage procedure. Non-treated, lavaged animals served as controls. After 75 min of ventilation, control values for PaO2 and PaCO2 were 13.3 +/- 6.8 and 6.8 +/- 2.3 kPa (mean +/- s.d.), respectively. The corresponding values in Group I of surfactant-treated animals were 52.9 +/- 7.7 and 4.4 +/- 1.1 kPa, in Group II 53.5 +/- 7.3 and 4.8 +/- 1.3 kPa (P less than 0.02-0.002). The two groups of surfactant-treated animals also had significantly improved alveolar air expansion in histological sections, as reflected by increased alveolar volume density (0.67 +/- 0.05 and 0.62 +/- 0.11 vs 0.45 +/- 0.08 in controls; P less than 0.002). The benefits of surfactant replacement in this experimental model were thus similar to those previously observed in animal models of neonatal surfactant deficiency as well as in babies with respiratory distress syndrome (RDS). Our data suggest that surfactant replacement might have a therapeutic effect also in clinical adult RDS.

Animals↗
PubMed1986

Correlations between physical and physiological properties of various preparations of lung surfactant.

The physical and physiological properties of natural surfactant were investigated after the addition of various synthetic lipids. Three types of surfactant were studied: 1. Bovine surfactant with rapid spreading (1.6 s) and a relatively high minimal surface tension during surface compression (16 mN/m). 2. The same surfactant enriched with dipalmitoylphosphatidylcholine (DPPC), tripalmitin, and palmitic acid showing slow spreading (55 s) and low minimal surface tension (5 mN/m). 3. The same surfactant enriched with DPPC and dipalmitin, showing rapid spreading (1.8 s) and low minimal surface tension (6 mN/m). The physiological properties of these surfactants were evaluated in immature newborn rabbits. All three preparations effectively improved lung expansion and stability in pressure-volume recordings, increased tidal volumes during artificial ventilation, and enhanced alveolar volume density in histological sections. The magnitude of the therapeutic effects was similar for non-enriched and enriched materials. Thus, wide variations in in vitro surface properties do not seem to influence the in vivo activity of the surfactant preparations.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

The role of the low-molecular weight (less than or equal to 15,000 daltons) apoproteins of pulmonary surfactant.

An artificial surfactant was prepared by combining synthetic dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol and the low-molecular weight (less than or equal to 15,000 daltons) surfactant apoproteins in the proportions 80:20:5. In the Wilhelmy balance, this surfactant formed a film with an equilibrium surface tension of 29 mN/m; surface tension was reduced to nearly zero during cyclic film compression, with effective respreadability during multiple compression-expansion cycles; similar surface properties were recorded with a pulsating bubble. When instilled into the airways of artificially ventilated immature newborn rabbits, the apoprotein-based artificial surfactant produced a five-fold increase in tidal volumes at insufflation pressure 25 cm H2O; this effect is similar to that obtained in previous experiments with natural surfactant phospholipids, administered in equal concentration (5 mg/ml). Higher concentration of the apoprotein-based surfactant could not be evaluated in vivo due to the high viscosity of the material. Systematic studies should be undertaken to find out whether an even more effective artificial surfactant could be prepared from the low-molecular weight apoproteins and other combinations of synthetic phospholipids.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1985

Leakage of protein in the immature rabbit lung; effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.

Albumins↗