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  • 1
    Electronic Resource
    Electronic Resource
    Effect of N-nitroso-N-methylurethane on gas exchange, lung compliance, and surfactant function of rabbits (1996)
    Springer
    Intensive care medicine 22 (1996), S. 345-352 
    Details
    ISSN: 1432-1238
    Keywords: Key words Pulmonary surfactants ; Respiratory distress syndrome ; adult ; N-nitroso-N-methylurethane ; Pulmonary compliance ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To define the effect of N-nitroso-N-methylurethane (NNNMU) on pulmonary gas exchange, compliance and the biochemical and functional properties of the lung surfactant system. Design: Four days after inducing lung injury, gas exchange and pulmonary compliance were studied and a bronchoalveolar lavage was taken. Setting: Experimental laboratory of a university department of medicine, division of pulmonary and critical care medicine. Animals: Ten rabbits after they had received an injection of NNNMU and five control animals. Interventions: Controlled mechanical ventilation and bronchoalveolar lavage. Measurements and results: Measurements of gas exchange (using the multiple inert gas elimination technique), hemodynamics and pulmonary compliance were performed during ventilatory and hemodynamic steady state. A bronchoalveolar lavage (BAL) was taken after sacrificing the animal. BAL samples were processed for cell count and biochemical and functional surfactant analysis. Animals injected with NNNMU developed mild, but significant reduction in PaO2, while maintaining eucapnia during spontaneous air breathing. ˙V/˙Q distributions and arterial blood gases were similar in all animals when ventilated mechanically with a fixed tidal volume. Compliance of the lung and phospholipid levels in lavage of NNNMU animals was significantly lower than in control animals (CON). Function of surfactant recovered from animals receiving NNNMU was decreased significantly where compared to CON. Thus, NNNMU resulted in a lowered lavage surfactant phospholipid content, impaired surfactant function, decreased compliance and hypoxemia during spontaneous ventilation. However, gas exchange was similar to that of control animals during mechanical ventilation. Conclusion: We conclude that NNNMU-induced gas exchange abnormalities present after 4 days are mild and are reversed by fixed volume mechanical ventilation despite marked alteration in surfactant function and lung compliance. These observations further define properties of a lung injury model that is of value in the study of surfactant replacement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700457
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of N-nitroso-N-methylurethane on gas exchange, lung compliance, and surfactant function of rabbits (1996)
    Springer
    Intensive care medicine 22 (1996), S. 345-352 
    Details
    ISSN: 1432-1238
    Keywords: Pulmonary surfactants ; Respiratory distress syndrome, adult ; N-nitroso-N-methylurethane ; Pulmonary compliance ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives To define the effect of N-nitroso-N-methylurethane (NNNMU) on pulmonary gas exchange, compliance and the biochemical and functional properties of the lung surfactant system. Design Four days after inducing lung injury, gas exchange and pulmonary compliance were studied and a bronchoalveolar lavage was taken. Setting Experimental laboratory of a university department of medicine, division of pulmonary and critical care medicine. Animals Ten rabbits after they had received an injection of NNNMU and five control animals. Interventions Controlled mechanical ventilation and bronchoalveolar lavage. Measurements and results Measurements of gas exchange (using the multiple inert gas elimination technique), hemodynamics and pulmonary compliance were performed during ventilatory and hemodynamic steady state. A bronchoalveolar lavage (BAL) was taken after sacrificing the animal. BAL samples were processed for cell count and biochemical and functional surfactant analysis. Animals injected with NNNMU developed mild, but significant reduction in PaO2, while maintaining eucapnia during spontaneous air breathing. $$\dot V/\dot Q$$ distributions and arterial blood gases were similar in all animals when ventilated mechanically with a fixed tidal volume. Compliance of the lung and phospholipid levels in lavage of NNNMU animals was significantly lower than in control animals (CON). Function of surfactant recovered from animals receiving NNNMU was decreased significantly where compared to CON. Thus, NNNMU resulted in a lowered lavage surfactant phospholipid content, impaired surfactant function, decreased compliance and hypoxemia during spontaneous ventilation. However, gas exchange was similar to that of control animals during mechanical ventilation. Conclusion We conclude that NNNMU-induced gas exchange abnormalities present after 4 days are mild and are reversed by fixed volume mechanical ventilation despite marked alteration in surfactant function and lung compliance. These observations further define properties of a lung injury model that is of value in the study of surfactant replacement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700457
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Oxidative Inactivation of Surfactants (1999)
    Springer
    Lung 177 (1999), S. 179-189 
    Details
    ISSN: 1432-1750
    Keywords: Key words: Lipid peroxidation—Protein carbonylation—Pulmonary surfactant—Reactive oxygen species—Surfactant inactivation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL4 surfactant (KL4). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO−) or 0.5 mM hypochlorous acid (OCl−), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant 〉 KL4 〉 NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p 〈 0.01) but lower concentration of malondialdehyde (p 〈 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL4 than in beractant (p 〈 0.05). Surface area cycling for 24 h with 2 mM ONOO− or 0.5 mM OCl− caused both beractant and KL4 to increase the proportion of light subtypes from 8–10% to 26–29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74–91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007639
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  • 4
    Electronic Resource
    Electronic Resource
    Inhibitory Effects of Oxyradicals on Surfactant Function: Utilizing in Vitro Fenton Reaction (1998)
    Springer
    Lung 176 (1998), S. 63-72 
    Details
    ISSN: 1432-1750
    Keywords: Key words: Surfactant function—Fenton effect— ; OH radical—Iron/EDTA complex—Oxo-iron species.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The inhibitory effects of reactive oxygen species (ROS) on the surface tension-lowering abilities of three surfactants were compared: natural lung surfactant (NLS), KL4 surfactant containing synthetic peptide resembling the hydrophobic/hydrophilic domains of SP-B in an aqueous dispersion of phospholipids, and Survanta® (SUR) containing SP-B and SP-C. The inhibitory concentrations of Fenton reactants (i.e. 0.65 mM FeCl2, 0.65 mM EDTA, 30 mM H2O2), deduced from dose-response plots of FeCl2 on minimum surface tension (MST) of SUR, were used to assess the Fenton effect on biophysical properties of various surfactants. Neither H2O2 (30 mM) nor FeCl2 with EDTA (both 0.65 mM) alone affected surfactant function, but when mixed together significantly increased (p 〈 0.01) the MST of SUR compared with KL4 (p 〈 0.05) in a FeCl2 concentration-dependent manner. This effect on NLS was not significant (p= 0.05) at similar phospholipid concentrations. Also, the range of increases in surface adsorption in mN/m at equilibrium surface tension (EST) was 27–40 for SUR, 36–44 for KL4, and 24–25 for NLS. We speculate that the presence of SP-A and the catalase content in NLS may have protective effects on inactivation of NLS by ROS. We conclude that the in vitro Fenton effect could be a valuable test system for comparing the inactivation range of surfactants by oxyradicals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007592
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  • 5
    Electronic Resource
    Electronic Resource
    Severe intracranial hemorrhage and hydrocephalus in low-birthweight infants treated with CSF shunts (1987)
    Springer
    Child's nervous system 3 (1987), S. 110-113 
    Details
    ISSN: 1433-0350
    Keywords: Prematurity ; Hemorrhage ; Hydrocephalus ; CSF shunt ; Outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high-risk low-birth-weight newborn not uncommonly develops intracranial hemorrhage and intraventricular hemorrhage (ICH/IVH) from the immature state of the germinal matrix. Posthemorrhagic hydrocephalus may develop. Infants with small hemorrhages (grades I, II of Papile), with or without hydrocephalus have been shown to develop normally in 80%–90% of cases. There is limited information in the literature about the management and outcome of infants with more severe hemorrhages (grades III, IV of Papile), due to the dismal outlook as to their outcome in most centers. The current status and concerns as to the management of these infants is reviewed, and the aspects of neurosurgical and neonatal follow-up and outcome are described. A significant number of these infants have severe handicaps, which are primarily motor. However, a group of infants is noted who have normal intellectual performance despite varying degrees of motor handicaps: 18% have normal intellectual and motor development. In the current series predictors of poorest outcome are the presence of grade IV hemorrhage and/or seizures. The vast majority of the grades III and IV hemorrhages develop hydrocephalus that is a complex management issue for the neurosurgeon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271136
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  • 6
    Electronic Resource
    Electronic Resource
    The influence of pH on surface properties of lung surfactants (1995)
    Springer
    Lung 173 (1995), S. 243-254 
    Details
    ISSN: 1432-1750
    Keywords: pH effect ; Ca2+ ; Surface adsorption ; Interface ; Protons ; Polar ionizable groups ; Transition temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Protein-lipid interactions at air-liquid interfaces are dependent on electrostatic charges, cations, anions, distribution of protons, and surface potential, which are influenced by pH changes. All of these factors may affect lung surfactant function. To verify the pH dependence of surface activity of pulmonary surfactant, we studied the in vitro effects of pH and Ca2+ on the surface tension-lowering abilities of various surfactants in an oscillating bubble surfactometer. Surface tension measurements were made of mixtures at known pHs or after the replacement of the subphase fluid of surfactant films with buffered saline at various pH values. At the pH range 4.0–7.0, the average equilibrium surface tension (EST)/minimum surface tension (MST) for natural surfactants human amniotic fluid and natural lung surfactant from rabbit lung lavage was 24/2 mN/m. At the same pH range, Exosurf and phospholipids alone had an EST/MST of 44/25 and 44/12 mN/m, respectively. Survanta (SUR) containing SP-B and SP-C and a phospholipid surfactant (KL4) containing a leucine/lysine peptide had an EST/MST of 29/5 and 36/3, respectively. Alkalinization of the subphase (pH 〉 7.4) significantly decreased the surface tension-lowering ability of SUR (P 〈 0.01) and to a lesser extent that of KL4 surfactant (P 〈 0.05), but natural lung surfactants were not significantly affected over a pH range of 3–7.5. These data demonstrate that natural surfactants maintain their optimal surface activities over a broader pH range than do the commercial products because of a lack of SP-A. Careful monitoring of the pH for optimal surface activity is recommended when evaluating surfactant function and the effects of specific inhibitors on this function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181876
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  • 7
    Electronic Resource
    Electronic Resource
    Characterization of Surfactant Subtypes of Beractant and a Synthetic Peptide Containing Surfactant KL4 following Surface Area Cycling and Addition of Fibrinogen (1997)
    Springer
    Lung 175 (1997), S. 225 -233 
    Details
    ISSN: 1432-1750
    Keywords: Key words: Surfactant inhibition—Surfactant subtype—Surfactant metabolism—Surface area cycling—SP-B-like peptide.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Surfactant is not a homogeneous material and can be separated into subtypes. Subtype conversion is clinically important because it is thought to occur naturally and because surface activity varies depending on the subtype. Fibrinogen, a naturally occurring serum protein, is known to affect this conversion. In this study we studied two surfactants, beractant and KL4, to examine their subtype characteristics. Surface area cycling, an in vitro method, was used in conjunction with sucrose gradient ultracentrifugation to separate subtypes in both surfactants. Activity, expressed as minimum surface tension of these subtypes, was measured using a pulsating bubble surfactometer. The effect of fibrinogen on subtype conversion and subsequent change in activity was elucidated. Our results indicate that following surface area cycling, beractant and KL4 have different subtypes and different responses to fibrinogen. Cycling of beractant resulted in two bands, representing a heavy and a light subtype. In the presence of fibrinogen, cycling resulted in two separate heavy subtypes. Cycling of KL4 surfactant also yielded light and heavy subtypes. However, in the presence of fibrinogen, cycling of KL4 resulted in ultraheavy subtypes. These ultraheavy subtypes retained minimum surface tension comparable to that of native KL4 surfactant. We conclude that these two surfactant preparations have different subtype conversions when subjected to surface area cycling and in the presence of fibrinogen. These conversions result in different activities toward lowering surface tension. We speculate that endogenous fibrinogen will also affect these two surfactants differently in vivo and thus affect their clinical effectiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007569
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