The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion

Abstract

BackgroundCurrently, 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+.MethodsTwelve 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.ResultsBAL 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.ConclusionIn 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.

In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633

“…Lucinactant is an SP-B-based synthetic surfactant composed of a phospholipid mixture and sinapultide, a leucine-and lysine-reach peptide aimed at mimicking SP-B function (17). Synsurf is a surfactant consisting of a phospholipids mixture and two polypeptides: poly-l-lysine electrostatically complexed with poly-l-glutamic acid (18).…”

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

“…The recently developed Synsurf was also tested earlier, in vivo in an adult rabbit saline-lavaged model 8. In that study, we showed significant improvement in oxygenation and pulmonary shunt in the group of animals treated with Synsurf.…”

“…Synsurf was prepared as described previously 8. Briefly, dipalmitoylphosphatidylcholine (DPPC), hexadecanol, and phosphatidylglycerol were mixed in a 10:1.1:1 ratio (w/w) in chloroform.…”

“…In 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 8. Our objective in the present 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.…”

“…Post hoc analysis of data from one study showed better survival using a high initial dose of Curosurf® (Chiesi Farmaceutici SpA, Parma, Italy) when compared with Survanta® (Abbott Laboratories, Abbott Park, North Chicago, IL, USA) 7. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested 8–10. A new-generation synthetic surfactant that contains a peptide mimicking the action of SP-B, Surfaxin (Discovery Laboratories, Warrington, PA, USA), performed better than a protein-free synthetic surfactant (Exosurf; GlaxoKlineSmith, Brentford, UK), and similarly to animal-derived surfactants (Survanta® and Curosurf®) 11.…”