Aerosolized surfactant in lung‐lavaged adult rats: factors influencing the therapeutic response

Bahlmann, Hans; Sun, Bo; Nilsson, Gunnar; Curstedt, Tore; Robertson, Bengt

doi:10.1034/j.1399-6576.2000.00521.x

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…The intubated preterm lamb model has been considered the gold standard model to study nRDS[23, 25, 27, 29], because the primary surfactant deficiency in the lambs adequately resembles human nRDS. The induction of lung injury by repeated BALs has also been used extensively as a model of acute lung-injury in the contest of RDS[12, 17, 18, 22, 44]. Nevertheless, the majority of these studies were performed during tracheal intubation and mechanical ventilation with full control of the airway.…”

Section: Discussionmentioning

confidence: 99%

“…On one hand, the depletion of the intrapulmonary surfactant pools by repeated bronco-alveolar lavages (BALs) with saline solution has been frequently used in juvenile as well as in adult rats[17, 18], rabbits[19, 20], and pigs[21, 22], among others, to implement successful animal models of acute pulmonary failure in the context of RDS. On the other hand, the intubated premature lamb has been the gold standard animal model to study the pathogenesis and the treatments of nRDS for many decades.…”

Section: Introductionmentioning

confidence: 99%

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Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

et al. 2017

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Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

et al. 2017

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“…Multiple studies have reported respiratory improvement with surfactant aerosol in animals with surfactant deficiency or dysfunction, 131,135,153,[155][156][157][158][159][160][161][162][163] although other aerosol studies have been less positive. [164][165][166][167] Several animal studies have directly compared aerosolization to tracheal instillation, and reported that aerosolization can have equal or greater effectiveness, 131,155,159 whereas others have found that instillation is more effective than aerosolization. 131,165,168 An example illustrating the need for further clarity on this issue is the study by Lewis et al 131 In lung-lavaged sheep, exogenous bovine lung extract surfactant was effective when instilled but ineffective when aerosolized, whereas beractant in the same animal model was more effective when aerosolized than when instilled.…”

Section: Animal Studies Of Surfactantmentioning

confidence: 99%

“…[164][165][166][167] Several animal studies have directly compared aerosolization to tracheal instillation, and reported that aerosolization can have equal or greater effectiveness, 131,155,159 whereas others have found that instillation is more effective than aerosolization. 131,165,168 An example illustrating the need for further clarity on this issue is the study by Lewis et al 131 In lung-lavaged sheep, exogenous bovine lung extract surfactant was effective when instilled but ineffective when aerosolized, whereas beractant in the same animal model was more effective when aerosolized than when instilled. Clinical studies with aerosolized surfactant have in general not had impressive results.…”

Section: Animal Studies Of Surfactantmentioning

confidence: 99%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Key words: surfactant; infant respiratory distress syndrome; RDS; acute lung injury; ALI; acute respiratory distress syndrome; ARDS; neonatal. [Respir Care 2011;56(9):1369 -1386.

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“…In these experiments we used the lavaged rat model because of its relative simplicity, stability and reproducibility [19,23,27]. Measures of gas exchange, pulmonary mechanics and capillary leak are all obtained in single experiments, and these are not possible in many newborn laboratory animals because of their small size.…”

Section: Discussionmentioning

confidence: 99%

Surfactant with SP-B and SP-C Analogues Improves Lung Function in Surfactant-Deficient Rats

et al. 2002

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The use of mammalian lung surfactant extracts has sharply reduced mortality and morbidity from respiratory distress syndrome in premature infants. Synthesis of surfactant protein B and C (SP-B and SP-C) analogues may lead the way to a synthetic surfactant preparation. Dimeric SP-B_1–25 (dSP-B_1–25) is based on the N-terminal domain of human SP-B and SP-Cfc is a modified human SP-C in which a single phenylalanine is substituted for a palmitoylated cysteine residue in the N-terminal segment (Phe-4 > Cys-4 variant). We tested the effects of synthetic surfactants with 1 or 2% dSP-B_1–25 and 1% SP-Cfc on lung function in surfactant-deficient rats. Four experimental surfactant preparations were prepared by mixing 1% dSP-B_1–25, 2% dSP-B_1–25, 1% dSP-B_1–25 +1% SP-Cfc, and 2% dSP-B_1–25 +1% SP-Cfc with phospholipids (PL). PL and Survanta, a bovine lung extract, were controls. Groups of 8 rats were ventilated, lavaged until surfactant deficiency, and treated with 100 mg/kg surfactant. Arterial blood gas values and dynamic compliance were measured every 15 min and after 2 h of ventilation, the rats were killed and pressure-volume curves performed. Oxygenation improved quickly after instillation of surfactant with synthetic peptides and Survanta. Oxygenation and lung volumes were consistently higher in the 2% than in the 1% dSP-B_1–25 groups. Addition of 1% SP-Cfc to the synthetic surfactants further improved oxygenation and lung volume, but to a lesser extent than increasing the dSP-B_1–25 content from 1 to 2%. These data indicate that improvements in oxygenation and lung volume in lavaged rats are dependent on the concentration of dSP-B_1–25 in the surfactant preparation and that the presence of SP-Cfc has a relative minor effect on these parameters.

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Aerosolized surfactant in lung‐lavaged adult rats: factors influencing the therapeutic response

Cited by 18 publications

References 31 publications

Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

The Future of Exogenous Surfactant Therapy

Surfactant with SP-B and SP-C Analogues Improves Lung Function in Surfactant-Deficient Rats

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