The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion
| dc.contributor.author | Van Zyl, Johann M. | |
| dc.contributor.author | Smith, Johan | |
| dc.contributor.author | Hawtrey, Arthur | |
| dc.date.accessioned | 2013-05-08T05:52:15Z | |
| dc.date.available | 2013-05-08T05:52:15Z | |
| dc.date.issued | 2013-03 | |
| dc.description | Publication of this article was funded by the Stellenbosch University Open Access Fund. | en_ZA |
| dc.description | The original publication is available at http://www.dovepress.com/drug-design-development-and-therapy-journal | en_ZA |
| dc.description.abstract | Background: Currently, a new generation of synthetic pulmonary surfactants is being developed that may eventually replace animal-derived surfactants used in the treatment of respiratory distress syndrome. Enlightened by this, we prepared a synthetic peptide-containing surfactant (Synsurf) consisting of phospholipids and poly-l-lysine electrostatically bonded to poly-l-glutamic acid. Our objective in this study was to investigate if bronchoalveolar lavage (BAL)-induced acute lung injury and surfactant deficiency with accompanying hypoxemia and increased alveolar and physiological dead space is restored to its prelavage condition by surfactant replacement with Synsurf, a generic prepared Exosurf, and a generic Exosurf containing Ca²⁺. Methods: Twelve adult New Zealand white rabbits receiving conventional mechanical ventilation underwent repeated BAL to create acute lung injury and surfactant-deficient lung disease. Synthetic surfactants were then administered and their effects assessed at specified time points over 5 hours. The variables assessed before and after lavage and surfactant treatment included alveolar and physiological dead space, dead space/tidal volume ratio, arterial end-tidal carbon dioxide tension (PCO₂) difference (mainstream capnography), arterial blood gas analysis, calculated shunt, and oxygen ratios. Results: BAL led to acute lung injury characterized by an increasing arterial PCO₂ and a simultaneous increase of alveolar and physiological dead space/tidal volume ratio with no intergroup differences. Arterial end-tidal PCO₂ and dead space/tidal volume ratio correlated in the Synsurf, generic Exosurf and generic Exosurf containing Ca²⁺ groups. A significant and sustained improvement in systemic oxygenation occurred from time point 180 minutes onward in animals treated with Synsurf compared to the other two groups (P ˂ 0.001). A statistically significant decrease in pulmonary shunt (P ˂ 0.001) was found for the Synsurf-treated group of animals, as well as radiographic improvement in three out of four animals in that group. Conclusion: In general, surfactant-replacement therapy in the animals did not fully restore the lung to its prelavage condition. However, our data show that the formulated surfactant Synsurf improves oxygenation by lowering pulmonary shunt. | en_ZA |
| dc.description.sponsorship | Stellenbosch University Open Access Fund | en_ZA |
| dc.description.version | Publishers' version | en_ZA |
| dc.format.extent | 10 p. | |
| dc.identifier.citation | Van Zyl, J. M., Smith, J. & Hawtrey, A.O. 2013. The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion. Drug Design, Development and Therapy, 7,139-148, doi:10.2147/DDDT.S40622. | en_ZA |
| dc.identifier.issn | 1177-8881 (print) | |
| dc.identifier.issn | 1177-8881 (online) | |
| dc.identifier.other | doi:10.2147/DDDT.S40622 | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/80729 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Dovepress | en_ZA |
| dc.rights.holder | Authors retain copyright | en_ZA |
| dc.subject | Synthetic pulmonary surfactants | en_ZA |
| dc.subject | Surface active agents | en_ZA |
| dc.subject | Respiratory distress syndrome | en_ZA |
| dc.title | The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion | en_ZA |
| dc.type | Article | en_ZA |