Surfactant treatment before first breath for respiratory distress syndrome in preterm lambs: comparison of a peptide-containing synthetic lung surfactant with porcine-derived surfactant

Abstract

BackgroundIn a recent study utilizing a saline-lavaged adult rabbit model, we described a significant improvement in systemic oxygenation and pulmonary shunt after the instillation of a novel synthetic peptide-containing surfactant, Synsurf. Respiratory distress syndrome in the preterm lamb more closely resembles that of the human infant, as their blood gas, pH values, and lung mechanics deteriorate dramatically from birth despite ventilator support. Moreover, premature lambs have lungs which are mechanically unstable, with the advantage of being able to measure multiple variables over extended periods. Our objective in this study was to investigate if Synsurf leads to improved systemic oxygenation, lung mechanics, and histology in comparison to the commercially available porcine-derived lung surfactant Curosurf® when administered before first breath in a preterm lamb model.Materials and methodsA Cesarean section was performed under general anesthesia on 18 time-dated pregnant Dohne Merino ewes at 129–130 days gestation. The premature lambs were delivered and ventilated with an expiratory tidal volume of 6–8 mL/kg for the first 30 minutes and thereafter at 8–10 mL/kg. In a randomized controlled trial, the two surfactants tested were Synsurf and Curosurf®, both at a dose of 100 mg/kg phospholipids (1,2-dipalmitoyl-L-α-phosphatidylcholine; 90% in Synsurf, 40% in Curosurf®). A control group of animals was treated with normal saline. Measurements of physiological variables, blood gases, and lung mechanics were made before and after surfactant and saline replacement and at 15, 30, 45, 60, 90, 120, 180, 240 and 300 minutes after treatment. The study continued for 5 hours.ResultsSurfactant treatment led to a significant improvement in oxygenation within 30 minutes, with the Synsurf group and the Curosurf® group having significantly higher ratios between arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2; P = 0.021) compared to that of the control (saline-treated) animals. Dynamic compliance improved in the three groups over time, with no intergroup differences. All of the surfactant-treated animals survived, and one in the saline group died before the study ended. Histology between groups was not different, showing mild–moderate injury patterns.Discussion: Treatment with surfactants before first breath clearly resulted in improved systemic oxygenation within 30 minutes of instillation. Both Synsurf- and Curosurf®-treated animals experienced similar and more sustained improvement in oxygenation and decreased calculated shunt compared to saline-treated animals.

Deposition and transport of linezolid mediated by a synthetic surfactant Synsurf^® within a pressurized metered dose inhaler: a Calu-3 model

“…Synsurf consists of a mixture of DPPC (saturated lipid) combined with 10% phosphatidylglycerol (contains unsaturated fatty acids) and the nonionic detergent tyloxapol as well as 1-hexadecanol as a spreading agent. 11 In addition to the above compounds, prep 1 contained linezolid and prep contained 2% by weight cholesterol (neutral lipid) and linezolid. In natural human pulmonary surfactant, cholesterol is present between 5% and 10% weight of the lipid components with no inhibitory effect on surface tension as seen with supra-physiological concentrations in adult respiratory distress syndrome.…”

“…10 Its efficacy proved to be similar to that of the commercially available naturally derived surfactants, that is, Curosurf ® , in a preterm lamb model. 11 …”

Synthetic surfactants with SP‐B and SP‐C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases

“…Finally, attempts have been made to entirely avoid the non-polar character of surfactant protein analogues, for example, by mixing polylysine and polyglutamic acid with synthetic phospholipids. The resulting synthetic surfactant has shown effects in preterm and surfactant depleted animal models of RDS, which were comparable to those of animal-derived surfactant preparations [212,213]. Chemical synthesis of SP-C analogues is feasible and the synthetic surfactant CHF5633 that is currently in clinical trials for neonatal RDS contains synthetic SP-C33Leu [214,215].…”

Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14+ Monocytes

“…These preparations containing variable amounts of lipids, mainly dipalmitoylphosphatidylcholine (DPPC), and residual hydrophobic surfactant proteins (SP)-B and SP-C, are very effective, but supplies are limited. Development and introduction of new generation synthetic surfactants is a promising approach to further improve surfactant replacement therapy and to widen indications [ 8 , 13 – 17 ]. In contrast to natural surfactants, synthetic surfactants may have standardized composition, increased resistance against inactivation, and may avoid the need for animal reservoir.…”