Surfactant reduces extravascular lung water and invasion of polymorphonuclear leukocytes into the lung in a piglet model of airway lavage

Krause, Martín; Wiemann, Tina; Reisner, Anja; Orlowska-Volk, Marzenna; Köhler, Heike; Ankermann, Tobias

doi:10.1016/j.pupt.2004.11.003

Cited by 25 publications

(25 citation statements)

References 38 publications

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“…The proinflammatory mediators IL-6 and IL-8 are chemokines causing neutrophil infiltration and exaggerated systemic inflammation (35). It has previously been demonstrated that elevated IL-6 and IL-8 levels in vivo can predict chronic lung disease in preterm infants (36,37).…”

Section: Discussionmentioning

confidence: 99%

KL4-Surfactant (Lucinactant) Protects Human Airway Epithelium from Hyperoxia

et al. 2008

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Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air-liquid interface were treated apically with 140 L of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O 2 /5% CO 2 for 24 or 72 h. Transepithelial resistance (TER; p Ͻ 0.001) and cell viability (p Ͻ 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant (p Ͻ 0.001). Surfactant treated groups secreted less IL-8 than saline (p Ͻ 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant (p Ͻ 0.001). P reterm birth is complicated by respiratory distress syndrome (RDS), a condition that threatens survival in this population. In the preterm infant, decreased lung compliance and neonatal RDS are related to deficiencies in the lung surfactant pool (1). In addition, deficiencies in antioxidants (2,3) and antiinflammatory modulators (4,5) potentially worsen RDS and lead to development of chronic lung disease, most notably bronchopulmonary dysplasia (BPD).RDS necessitates life-sustaining treatment with supplemental oxygen and mechanical ventilation. These therapies independently have been shown to injure the lung and are implicated in the pathogenesis of BPD (6). Surfactant replacement therapy has become standard of care for preventing and treating RDS (7,8). Although effective at acutely improving lung mechanics, oxygenation, and reducing mortality, surfactant replacement therapy has been linked to exaggerated inflammatory responses (9,10) and has not significantly impacted the incidence of BPD.Lung inflammation in RDS is central to the pathogenesis of BPD (11), and is a complex process involving upregulation of proinflammatory cytokines, including IL-6 and IL-8, and influx of inflammatory cells to the airways (7). Neonatal deficiencies in antioxidants and antiinflammatory modulators favor a proinflammatory process that furthers epithelial injury and pulmonary remodeling by activated matrix modeling proteins such as matrix metalloproteinases (MMPs). MMPs released by injured cells contribute to greater microvascular permeability and release matrix components that function as proinflammatory mediators or growth factors to further inflammation and remodeling (12). MMP activity in the lung and airways has been associated with fibrotic lung diseases, including BPD (13,14).Surfactant-associated proteins play important roles in maintaining pulmonary homeostasis. Deficiency of surfactantassociated proteins causes severe respiratory distress, and in the case of surfactant protein B (SP-B), is incompatible with life (15). SP-B is a hydrophob...

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Section: Discussionmentioning

confidence: 99%

KL4-Surfactant (Lucinactant) Protects Human Airway Epithelium from Hyperoxia

et al. 2008

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“…One of the reasons could be due to the age of the piglets (12 to 72 h) in the present study. Recently, Krause et al (10) reported EVLW values obtained by single thermodilution and by gravimetric assessment in 2-to 10-day-old piglets (weighing 2700 ± 700 g) after pulmonary edema induced by repeated airway lavages, although the basal EVLW values were not reported. Other species such as rabbits have higher mean EVLW values than piglets, with 4-day-old rabbits having 83% LW content compared to wet lung weight, higher than that observed in the present study (33).…”

Section: Methodological Validation For the Assessment Of Evlwmentioning

confidence: 99%

“…The specific aim of this study was to monitor EVLW and hemodynamics after meconium aspiration in newborn piglets, exploring the utility of the in vivo monitoring of newborn acute respiratory failure and to evaluate the hemodynamic response after the oral administration of sildenafil, as it is usually administered to newborn babies. To address these questions, the validation of the thermodilution method in animals weighing 1300 to 2700 g was required since it has not been reported previously (10).…”

Section: Introductionmentioning

confidence: 99%

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Silvera

Blasina

Vaamonde

et al. 2011

Braz J Med Biol Res

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“…Recently, Krause et al [7] published data from mechanically ventilated neonatal piglets with saline lavageinduced lung injury evaluating the impact of exogenous surfactant on extravascular lung water and on lung inflammation. They found evidence for decreased extravascular lung water and decreased infiltration of polymorphonuclear leukocytes (PMNs) without significant changes in acute phase cytokines after 6 h of ventilation.…”

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confidence: 99%

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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Surfactant reduces extravascular lung water and invasion of polymorphonuclear leukocytes into the lung in a piglet model of airway lavage

Cited by 25 publications

References 38 publications

KL4-Surfactant (Lucinactant) Protects Human Airway Epithelium from Hyperoxia

KL4-Surfactant (Lucinactant) Protects Human Airway Epithelium from Hyperoxia

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

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

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