Effect of exogenous surfactant instillation on experimental acute lung injury

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.

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Surfactant protein A regulates surfactant phospholipid clearance after LPS-induced injury in vivo

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00418.2001 ◽

2002 ◽

Vol 283 (1) ◽

pp. L76-L85 ◽

Cited By ~ 11

Author(s):

Omar A. Quintero ◽

Thomas R. Korfhagen ◽

Jo Rae Wright

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Pulmonary Surfactant ◽

Protein A ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Wild Type ◽

Surfactant Phospholipids

Previous in vitro studies have suggested that surfactant protein A (SP-A) may play a role in pulmonary surfactant homeostasis by mediating surfactant secretion and clearance. However, mice made deficient in SP-A [SP-A (−/−) animals] have relatively normal levels of surfactant compared with wild-type SP-A (+/+) animals. We hypothesize that SP-A may play a role in surfactant homeostasis after acute lung injury. Bacterial lipopolysaccharide was instilled into the lungs of SP-A (−/−) mice and SP-A (+/+) mice to induce injury. Surfactant phospholipid levels were increased 1.6-fold in injured SP-A (−/−) animals, although injury did not alter [3H]choline or [14C]palmitate incorporation into dipalmitoylphosphatidylcholine (DPPC), suggesting no change in surfactant synthesis/secretion 12 h after injury. Clearance of [3H]DPPC from the lungs of injured SP-A (−/−) animals was decreased by ∼40%. Instillation of 50 μg of exogenous SP-A rescued both the clearance defect and the increased phospholipid defect in injured SP-A (−/−) animals, suggesting that SP-A may play a role in regulating clearance of surfactant phospholipids after acute lung injury.

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The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine

Expert Review of Respiratory Medicine ◽

10.1586/ers.10.71 ◽

2010 ◽

Vol 4 (6) ◽

pp. 773-783 ◽

Cited By ~ 137

Author(s):

Hong Chen ◽

Chunxue Bai ◽

Xiangdong Wang

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Respiratory Medicine ◽

Injury Model ◽

Lung Injury Model

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PULMONARY FIBROBLAST FUNCTION IN AN ACUTE LUNG INJURY MODEL

Journal of Trauma and Acute Care Surgery ◽

10.1097/00005373-199407000-00052 ◽

1994 ◽

Vol 37 (1) ◽

pp. 156

Author(s):

Andrew Mikulaschek ◽

Stantey Z Trooskin ◽

Allen Nonn ◽

Jason Winfield

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Injury Model ◽

Lung Injury Model ◽

Pulmonary Fibroblast

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Derivation of recruitment function from the pressure–volume curve in an acute lung injury model

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2014.09.008 ◽

2015 ◽

Vol 205 ◽

pp. 16-20 ◽

Cited By ~ 6

Author(s):

Yoshihiro Uzawa ◽

Mikiya Otsuji ◽

Koichi Nakazawa ◽

Wei Fan ◽

Yoshitsugu Yamada

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Volume Curve ◽

Pressure Volume Curve ◽

Injury Model ◽

Lung Injury Model

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High oxygen concentrations predispose mouse lungsto the deleterious effects of high stretch ventilation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00619.2002 ◽

2003 ◽

Vol 94 (3) ◽

pp. 975-982 ◽

Cited By ~ 46

Author(s):

Timothy C. Bailey ◽

Erica L. Martin ◽

Lin Zhao ◽

Ruud A. W. Veldhuizen

Keyword(s):

Mechanical Ventilation ◽

Acute Lung Injury ◽

Lung Function ◽

Lung Injury ◽

Inflammatory Cytokines ◽

Pulmonary Surfactant ◽

Ex Vivo ◽

Lung Stretch ◽

Isolated Lungs ◽

Mechanical Ventilation Group

Mechanical ventilation is a necessary intervention for patients with acute lung injury. However, mechanical ventilation can propagate acute lung injury and increase systemic inflammation. The exposure to >21% oxygen is often associated with mechanical ventilation yet has not been examined within the context of lung stretch. We hypothesized that mice exposed to >90% oxygen will be more susceptible to the deleterious effects of high stretch mechanical ventilation. C57B1/6 mice were randomized into 48-h exposure of 21 or >90% oxygen; mice were then killed, and isolated lungs were randomized into a nonstretch or an ex vivo, high-stretch mechanical ventilation group. Lungs were assessed for compliance and lavaged for surfactant analysis, and cytokine measurements or lungs were homogenized for surfactant-associated protein analysis. Mice exposed to >90% oxygen + stretch had significantly lower compliance, altered pulmonary surfactant, and increased inflammatory cytokines compared with all other groups. Our conclusion is that 48 h of >90% oxygen and high-stretch mechanical ventilation deleteriously affect lung function to a greater degree than stretch alone.

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Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.3.l512 ◽

2001 ◽

Vol 280 (3) ◽

pp. L512-L518 ◽

Cited By ~ 24

Author(s):

Nicholas W. Lukacs ◽

M. Michael Glovsky ◽

Peter A. Ward

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Bronchoalveolar Lavage ◽

Immune Complex ◽

Airway Hyperreactivity ◽

Lung Model ◽

Bronchial Inflammation ◽

Lung Injury Model ◽

Airway Responses ◽

Deficient Mice

Bronchoconstriction responses in the airway are caused by multiple insults and are the hallmark symptom in asthma. In an acute lung injury model in mice, IgG immune complex deposition elicited severe airway hyperreactivity that peaked by 1 h, was maintained at 4 h, and was resolved by 24 h. The depletion of complement with cobra venom factor (CVF) markedly reduced the hyperreactive airway responses, suggesting that complement played an important role in the response. Blockade of C5a with specific antisera also significantly reduced airway hyperreactivity in this acute lung model. Complement depletion by CVF treatment significantly reduced tumor necrosis factor and histamine levels in bronchoalveolar lavage fluids, correlating with reductions in airway hyperreactivity. To further examine the role of specific complement requirement, we initiated the immune complex response in C5-sufficient and C5-deficient congenic animals. The airway hyperreactivity response was partially reduced in the C5-deficient mice. Complement depletion with CVF attenuated airway hyperreactivity in the C5-sufficient mice but had a lesser effect on the airway hyperreactive response and histamine release in bronchoalveolar lavage fluids in C5-deficient mice. These data indicate that acute lung injury in mice after deposition of IgG immune complexes induced airway hyperreactivity that is C5 and C5a dependent.

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Fractal analysis of surfactant deposition in rabbit lungs

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.3.862 ◽

1995 ◽

Vol 78 (3) ◽

pp. 862-866 ◽

Cited By ~ 3

Author(s):

N. Gilliard ◽

D. Pappert ◽

R. G. Spragg

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Correlation Coefficient ◽

Fractal Analysis ◽

Coefficient Of Variation ◽

Surfactant Concentration ◽

Fractal Property ◽

Exogenous Surfactant ◽

Average Correlation

The effect of exogenous surfactant in the treatment of acute lung injury may depend on homogeneity of distribution of the material delivered. Analyses of distribution rely on sectioning the lung, determining surfactant concentration for each piece, and describing the variation in that value. Results of such analyses are influenced by how finely the lung is sectioned. We have reanalyzed data from prior experiments to determine whether the distribution of administered surfactant is fractal, that is, is independent of the scale of measurement. Lungs from animals receiving surfactant radiolabeled with [3H]dipalmitoylphosphatidylcholine were cut into 108 pieces, and the normalized radioactivity in each piece was determined. Sectioning of the lungs into different numbers of pieces (n = 2, 6, 12, 18, 36, 54, or 108) was simulated, and corresponding radioactivity contents were calculated. The coefficient of variation (CV) of these normalized values was then calculated for each scale of measurement (expressed as relative piece volume), and ln(CV) was plotted as a function of the logarithm of relative piece volume. These relationships were linear (average correlation coefficient = 0.96) for all animals, consistent with CV being a fractal property. We conclude that the intrapulmonary distribution of surfactant may be fractal and is therefore a property of the lung. This study demonstrates the utility of fractal analysis in describing the pulmonary distribution of substances introduced via the airway.

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