| 1. |
- Grossmann, G, et al.
(författare)
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Experimental neonatal respiratory failure induced by lysophosphatidylcholine: effect of surfactant treatment
- 1999
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 86:2, s. 633-640
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to characterize the toxic effects of lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various doses of lyso-PC (from 0 to 40 mg/kg) were administered to near-term newborn rabbits. Lung-thorax compliance during mechanical ventilation was significantly decreased by doses ≥10 mg/kg, and static lung volumes during deflation were decreased by doses ≥20 mg/kg. Using the same experimental model, we investigated the effects of modified porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC at birth and treated simultaneously with surfactant showed a satisfactory therapeutic response, whereas those treated after 30 min failed to respond. These animals also had a much larger leak of albumin into the air spaces and an elevated minimum surface tension of the lavage fluid in a pulsating bubble surfactometer, suggesting inactivation of the exogenous surfactant. Timing of surfactant administration may thus be essential for the therapeutic effect in this experimental model of acute lung injury.
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| 2. |
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| 3. |
- ROBERTSON, B, et al.
(författare)
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Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits
- 1995
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 68:3, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.
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| 4. |
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| 5. |
- Tashiro, K, et al.
(författare)
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Modified protocols for surfactant therapy in experimental meconium aspiration syndrome
- 2003
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 83:1, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50–75 mg kg<sup>–1</sup>) through the airways. When the PaO<sub>2</sub> had decreased to <20 kPa (mean ± SD 12 ± 3.9 kPa), the rats were randomly allocated to ten groups (G). G 6–10 underwent lung lavage with diluted Curosurf (5 mg ml<sup>–1</sup>, 20 ml kg<sup>–1</sup>), whereas G 1–5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg<sup>–1</sup>), and G 3 and 8 received Curosurf (100 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>); G 4 and 9 received Curosurf (200 mg kg<sup>–1</sup>), and G 5 and G 10 received Curosurf (200 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO<sub>2</sub> transiently increased to 30–40 kPa. In G 4, 5, 9, and 10, the PaO<sub>2</sub> remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg<sup>–1</sup>) was nevertheless required to optimize gas exchange.
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| 6. |
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| 7. |
- Ahlström, J. Zebialowicz, et al.
(författare)
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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
- 2019
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.
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| 8. |
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| 9. |
- Almlen, A, et al.
(författare)
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Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity
- 2007
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 92:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. <i>Objectives:</i> To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol (68:31, w/w). <i>Methods:</i> Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. <i>Results:</i> Preparations containing ≧1% SP-C33 achieve minimum surface tension <5 mN/m indicating good biophysical activity, and increase tidal volumes in premature rabbit fetuses to the same level as a modified natural surfactant preparation does. Alveolar patency at end expiration, as evaluated by measurement of lung gas volumes, histological assessment of alveolar expansion and determination of alveolar volume density, was lower in the animals treated with synthetic surfactant than in those receiving modified natural surfactant. <i>Conclusions:</i> These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
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