In vitro and in vivo intrapulmonary distribution of fluorescently labeled surfactant

Diemel, Robert V.; Walch, Monika; Haagsman, Henk P.; Pütz, G.

doi:10.1097/00003246-200205000-00020

Cited by 18 publications

(9 citation statements)

References 42 publications

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“…However, this large quantity delivery can result in flooding of the central airways and lead to increased airway resistance and worsening of hypoxemia. In animal models, intratracheal administration leads to poor surfactant deposition in the collapsed alveoli [55]. An alternative is sequential bronchoscopic administration, which has been evaluated in a number of uncontrolled studies.…”

Section: Possible Explanations For the Negative Results From Surfactamentioning

confidence: 99%

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

et al. 2012

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Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies. Surfactant dysfunction with quantitative and qualitative abnormalities of both phospholipids and proteins are characteristic of patients with ARDS. Exogenous surfactant replacement in animal models of ARDS and neonatal respiratory distress syndrome shows consistent improvements in gas exchange and survival. However, whilst some adult studies have shown improved oxygenation, no survival benefit has been demonstrated to date. This lack of clinical efficacy may be related to disease heterogeneity (where treatment responders may be obscured by nonresponders), limited understanding of surfactant biology in patients or an absence of therapeutic effect in this population. Crucially, the mechanism of lung injury in neonates is different from that in ARDS: surfactant inhibition by plasma constituents is a typical feature of ARDS, whereas the primary pathology in neonates is the deficiency of surfactant material due to reduced synthesis. Absence of phenotypic characterisation of patients, the lack of an ideal natural surfactant material with adequate surfactant proteins, coupled with uncertainty about optimal timing, dosing and delivery method are some of the limitations of published surfactant replacement clinical trials. Recent advances in stable isotope labelling of surfactant phospholipids coupled with analytical methods using electrospray ionisation mass spectrometry enable highly specific molecular assessment of phospholipid subclasses and synthetic rates that can be utilised for phenotypic characterisation and individualisation of exogenous surfactant replacement therapy. Exploring the clinical benefit of such an approach should be a priority for future ARDS research.

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Section: Possible Explanations For the Negative Results From Surfactamentioning

confidence: 99%

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

et al. 2012

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“…Taken together, these findings support regional differences in lung inflation, with spontaneous respiration during CPAP directed towards nondependent areas; the addition of SIMV worsened nondependent inflation. Regional distribution of surfactant has been described and may partially explain the differences noted [20] . But increased biochemical evidence of injury in the CPAP control animals who did not receive surfactant, taken together with the histologic injury differences, suggests that mechanical ventilation with SIMV also contributes.…”

Section: Discussionmentioning

confidence: 96%

Decreased Lung Injury after Surfactant in Piglets Treated with Continuous Positive Airway Pressure or Synchronized Intermittent Mandatory Ventilation

et al. 2007

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Background: Treatment with surfactant (S) decreases lung injury in paralyzed, mechanically ventilated animals. The use of nasal continuous positive airway pressure (CPAP) as an alternative to mechanical ventilation may further improve acute pulmonary outcomes. Objectives: To evaluate the effect of surfactant (+S, –S) and synchronized intermittent mandatory ventilation (SIMV) on lung morphology and inflammatory markers in 24 spontaneously breathing piglets treated with CPAP or SIMV after saline lavage-induced lung injury. Methods: After induction of lung injury, animals were randomized to CPAP–S, CPAP+S or SIMV+S and treated for 4 h. Physiologic parameters were continuously monitored. After treatment, animals were euthanized and lungs fixed. Bronchoalveolar lavage (BAL) samples were collected for neutrophil count and H₂O₂. Results: No physiologic differences were noted. BAL fluid from CPAP–S animals contained more neutrophils and more neutrophil H₂O₂ than fluid from the SIMV+S or CPAP+S groups (p < 0.05 or greater). Pathologic injury scores were higher in dependent lung regions from CPAP groups (p < 0.05). Injury pattern scores showed greater dependent alveolar inflammation in all (p < 0.02), with more dependent atelectasis in the CPAP groups (p < 0.01). Morphometrics showed less total open alveolar air space in nondependent regions of the SIMV+S group compared to CPAP groups (p < 0.001). Dependent regions showed less total open alveolar air space compared to nondependent regions in the CPAP groups (p < 0.001). Conclusions: Animals treated with surfactant prior to CPAP or SIMV had less acute lung injury. SIMV+S animals had less open air space in nondependent regions. This suggests, during early ventilatory support, surfactant administration may modulate pulmonary inflammation. CPAP alone without surfactant may not provide optimal pulmonary protection. The addition of mechanical breaths may alter and add to injury.

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“…We also used another assay that mimics some aspects of tracheal deposition of surfactant (subsurface transfer and subsequent surface adsorption) [29,30] …”

Section: Spreading Troughmentioning

confidence: 99%

Reductions of phospholipase A₂inhibition of pulmonary surfactant with hyaluronan

Iwanicki

Taeusch

2010

Experimental Lung Research

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In acute lung injuries, secretory phospholipase A(2) (sPLA(2)) inhibits surfactants by hydrolyzing phospholipids. Because hyaluronan (HA) reduces hydrolysis of phospholipids by sPLA(2), and because sPLA(2) inhibits surfactant in vitro, the authors hypothesized HA would reduce sPLA(2) inhibition. Surfactants were used alone or mixed with HA and/or sPLA(2) then tested for surface activity in 2 separate assays, or for sPLA(2) activity. Equilibrium surface pressures were identical for surfactant with or without HA. sPLA(2) inhibited surface activity but this inhibitory effect was reduced with HA by 14% in the spreading trough and by 63% in a modified bubble surfactometer. Hyaluronan caused a modest reduction (39%) of sPLA(2) breakdown of labeled phospholipid. Therefore hyaluronan reduces inhibition of surfactants by sPLA(2) in vitro, and reduces the activity of the enzyme.

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In vitro and in vivo intrapulmonary distribution of fluorescently labeled surfactant

Cited by 18 publications

References 42 publications

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

Decreased Lung Injury after Surfactant in Piglets Treated with Continuous Positive Airway Pressure or Synchronized Intermittent Mandatory Ventilation

Reductions of phospholipase A₂inhibition of pulmonary surfactant with hyaluronan

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In vitro and in vivo intrapulmonary distribution of fluorescently labeled surfactant

Cited by 18 publications

References 42 publications

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

Decreased Lung Injury after Surfactant in Piglets Treated with Continuous Positive Airway Pressure or Synchronized Intermittent Mandatory Ventilation

Reductions of phospholipase A2inhibition of pulmonary surfactant with hyaluronan

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Reductions of phospholipase A₂inhibition of pulmonary surfactant with hyaluronan