Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits.

Background: Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure.

Inactivation of pulmonary surfactant by silicone oil in vitro and in ventilated immature rabbits.

Objective: Surface activity of pulmonary surfactant is impaired by exposure to syringes lubricated with silicone oil (SO). These syringes are used daily in clinical practice.

Design: In vitro experiments were used for detection of SO, determination of surface activity, and semiquantitative measurement of surfactant protein (SP)-B and -C in SO/surfactant mixtures.

Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome.

Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of approximately 5 ml/kg after 30 min of ventilation.

Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity.

Background: Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5-1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development.

Polymyxin B/pulmonary surfactant mixtures have increased resistance to inactivation by meconium and reduce growth of gram-negative bacteria in vitro.

Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl2) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained.

Dextran or polyethylene glycol added to curosurf for treatment of meconium lung injury in rats.

Background: In experimental lung injuries, improvement of lung function after treatment with surfactant/polymer mixtures may depend on both type of polymer and the specific surfactant. In vitro studies suggest that dextran is more effective when mixed with Curosurf, and polyethylene glycol (PEG) is more effective when mixed with Survanta. We therefore wanted to find out whether these results held true in an animal model of acute lung injury.

Spontaneous breathing or mechanical ventilation alters lung compliance and tissue association of exogenous surfactant in preterm newborn rabbits.

In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation.

Influence of modified natural and synthetic surfactant preparations on bacterial killing by polymorphonuclear leucocytes.

In addition to its biophysical functions, surfactant plays an important role in pulmonary host defense. In this investigation we studied the influence of various commercially available surfactants on the phagocytosis of bacteria that are common pathogens in the neonatal period. Group B streptococci (GBS), Escherichia coli and Staphylococcus aureus were cultured with isolated human polymorphonuclear leucocytes (PMN) and non-specific serum in the presence or absence of different modified natural (Curosurf, Alveofact, Survanta) or totally synthetic, protein-free surfactant preparations (Exosurf, Pumactant).

Incomplete protection by prophylactic surfactant against the adverse effects of large lung inflations at birth in immature lambs.

Objective: To investigate whether preceding surfactant instillation prevents the harmful effect of large lung inflations at birth in immature lambs, and, if not, to find out for how long the immature lung remains sensitive to large inflations.

Design: In an exploratory study, 12 preterm lambs given surfactant at birth were randomized to receive five large lung inflations at four different times: at birth just before or immediately after surfactant treatment; at 10 min; or at 60 min of age. In a confirmatory study, 10 pairs of preterm lamb twins were all given surfactant before the first breath.

Intratracheal albumin reduces interleukin-8 in tracheobronchial aspirates in piglets after meconium aspiration.

Meconium aspiration induces pulmonary inflammation and reduces surfactant function. We hypothesized that albumin mixed with meconium attenuates pulmonary inflammation and improves surfactant function after meconium aspiration. We measured the concentration of free fatty acids (FFA) in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA:albumin ratio of 1:1.

Influence of partial liquid ventilation on bacterial growth and alveolar expansion in newborn rabbits with group B-streptococcal pneumonia.

Partial liquid ventilation (PLV) with perfluorocarbons has been considered as an alternative therapy for severe inflammatory lung disease. The present study was performed to test whether PLV influences bacterial growth and lung histology in a rabbit model of congenital pneumonia caused by group B streptococci. Near-term newborn rabbits were tracheotomized, inoculated via the airways with group B streptococci, and subsequently ventilated for 5 h with either PLV or conventional ventilation.

A synthetic surfactant based on a poly-Leu SP-C analog and phospholipids: effects on tidal volumes and lung gas volumes in ventilated immature newborn rabbits.

Available surfactants for treatment of respiratory distress syndrome in newborn infants are derived from animal lungs, which limits supply and poses a danger of propagating infectious material. Poly-Val-->poly-Leu analogs of surfactant protein (SP)-C can be synthesized in large quantities and exhibit surface activity similar to SP-C. Here, activity of synthetic surfactants containing a poly-Leu SP-C analog (SP-C33) was evaluated in ventilated premature newborn rabbits.

Modified protocols for surfactant therapy in experimental meconium aspiration syndrome.

In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50-75 mg kg(-1)) through the airways. When the PaO(2) had decreased to <20 kPa (mean +/- SD 12 +/- 3.

Syringes with rubber-coated plungers and inactivation of surfactant.

Injectable drugs are generally administered to newborns with 1 mL syringes. During in-vitro measurements of surface tension with a pulsating bubble surfactometer, we noticed that surfactant was inactivated after repeated aspiration into a 1 mL syringe with a rubber-coated plunger. Inactivation did not take place, however, when we used rubber-free two-part syringes with polyethylene pistons.