Effects of rSP-C Surfactant on Oxygenation and Histology in a Rat-Lung-Lavage Model of Acute Lung Injury

Häfner, Dietrich; Germann, Paul-Georg; Hauschke, Dieter

doi:10.1164/ajrccm.158.1.9712061

Cited by 60 publications

(45 citation statements)

References 25 publications

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“…Instillation of SP-C preparations into the lungs of preterm rabbits and lambs improved lung pressure volume curves and lung compliance (11). Similarly, SP-C-based synthetic surfactants improved lung compliance and oxygenation in adult rat and sheep lung injury models (12)(13)(14). When measurements of lung mechanics were evaluated at end expiration (low PEEP), the SP-C (Ϫ͞Ϫ) mice had only modest increases in airway and tissue resistance, whereas hysteresivity was reduced significantly in these animals.…”

Section: Discussionmentioning

confidence: 89%

“…Bovine surfactant preparations presently in clinical use contain phospholipids and are enriched in SP-C (8). A synthetic surfactant composed of dipalmitoyl-phosphatidylcholine, phosphatidylglycerol, and recombinant human SP-C restored lung compliance in premature sheep, rabbit, and adult animal models of acute lung injury (10)(11)(12)(13)(14). SP-C-based surfactant presently is being evaluated in clinical studies for the treatment of adult respiratory distress syndrome.…”

mentioning

confidence: 99%

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Altered stability of pulmonary surfactant in SP-C-deficient mice

Glasser

Burhans

Korfhagen

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

267

192

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

Altered stability of pulmonary surfactant in SP-C-deficient mice

Glasser

Burhans

Korfhagen

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

267

192

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“…Two important conceptual approaches being followed to develop synthetic exogenous surfactants are: (1) Combining human sequence recombinant proteins or synthetic amphipathic peptides with synthetic biological glycerophospholipids; and (2) combining synthetic amphipathic peptides with novel synthetic lipids designed to have favorable physicochemical properties such as high surface activity and structural resistance to inflammatory phospholipases during lung injury. Surfaxin® (KL4) [87,107,123,[189][190][191][192][193][194][195] and Venticute® (recombinant SPC surfactant) [26,[196][197][198][199][200][201] are two current examples of the first of these approaches (Table 3). However, the 21 amino acid KL4 peptide is only a very rough structural analog to native SP-B, and advances in peptide molecular modeling and synthesis technology support the feasibility of preparing new SP-B peptides with significantly greater sequence and molecular folding specificity, and correspondingly higher activity ( [202][203][204] for review).…”

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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“…3B), was used to prepare a synthetic surfactant. This synthetic surfactant improved the lung function in preterm rabbits and lambs [40], and also in animal models of acute lung injury where the effect on oxygenation and histology was studied [39] and compared with that of natural or synthetic surfactants [38]. The intratracheal instillation of this bacterially-expressed recombinant SP-C-based surfactant displayed no significant risk of an anaphylactic shock reaction in a guinea pig model of acute lung hypersensitivity [37].…”

mentioning

confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

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Effects of rSP-C Surfactant on Oxygenation and Histology in a Rat-Lung-Lavage Model of Acute Lung Injury

Cited by 60 publications

References 25 publications

Altered stability of pulmonary surfactant in SP-C-deficient mice

Altered stability of pulmonary surfactant in SP-C-deficient mice

Surfactant for Pediatric Acute Lung Injury

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

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