Resistance of Different Surfactant Preparations to Inactivation by Meconium

Abstract

A disease similar to acute respiratory distress syndrome may occur in neonates after aspiration of meconium. The aim of the study was to compare the inhibitory effects of human meconium on the following surfactant preparations suspended at a concentration of 2.5 mg/mL: Curosurf, Alveofact, Survanta, Exosurf, Pumactant, rabbit natural surfactant from bronchoalveolar lavage, and two synthetic surfactants based on recombinant surfactant protein-C (Venticute) or a leucine/lysine polypeptide. Minimum surface tension, determined with a pulsating bubble surfactometer, was increased Ͼ10 mN/m at meconium concentrations Ն0.04 mg/mL for Curosurf, Alveofact, or Survanta, Ն0.32 mg/mL for recombinant surfactant protein-C, Ն1.25 mg/mL for leucine/lysine polypeptide, and Ն20 mg/mL for rabbit natural surfactant. The protein-free synthetic surfactants Exosurf and Pumactant did not reach minimum surface tension Ͻ10 mN/m even in the absence of meconium. We conclude that surfactant activity is inhibited by meconium in a dose-dependent manner. Recombinant surfactant protein-C and leucine/lysine polypeptide surfactant were more resistant to inhibition than the modified natural surfactants Curosurf, Alveofact, or Survanta but less resistant than natural lavage surfactant containing surfactant protein-A. We speculate that recombinant hydrophobic surfactant proteins or synthetic analogs of these proteins can be used for the design of new surfactant preparations that are relatively resistant to inactivation and therefore suitable for treatment of acute respiratory distress syndrome. Surfactant deficiency has been recognized as the cause of RDS in premature infants, and treatment with modified natural surfactant preparations has considerably improved the prognosis of this disease (1). However, it has been realized that secondary surfactant deficiency caused by inactivation of the surfactant system may occur in patients with mature lungs. In ARDS (acute (adult) RDS), surfactant inhibitors may reach the alveolar space by inhalation or aspiration, and proteins such as albumin or fibrinogen may leak into the airways as a consequence of increased vascular permeability caused by pneumonia, for example (2-4). To treat ARDS in such a patient, relatively large doses of surfactant need to be instilled to overcome the amount of surfactant inhibitors present in the airways (5). Thus, surfactant preparations used for treatment of ARDS should be relatively resistant to inactivation (6). Recent advances in the synthesis and heterologous expression of lung SPs or their analogs might allow the production of designer surfactants (7) that are highly resistant to surfactant inhibitors. Under ARDS-like conditions, such preparations may be superior to currently available modified natural surfactants.Aspiration of meconium can result in severe respiratory failure in term neonates (8 -10). Surfactant inactivation is believed to play a key role in the pathophysiology of MAS, and inhibition of the surface tension-lowering activity of surfactant by meconium has been...

Polymyxin B/Pulmonary Surfactant Mixtures Have Increased Resistance to Inactivation by Meconium and Reduce Growth of Gram-Negative Bacteria In Vitro

“…Pilot studies using intratracheal doses of 50 -200 mg/kg of exogenous pulmonary surfactant as well as a controlled, randomized clinical study showed improved oxygenation of neonates with MAS receiving repeated high doses of surfactant (3). However, modified natural surfactants containing hydrophobic surfactant proteins B (SP-B) and C (SP-C) were more sensitive to inactivation by meconium than synthetic surfactant preparations based on artificial peptides such as SP-C analogues or the simplified peptide KL 4 (4). Thus, development of surfactants that are resistant to inactivation might be useful (5).…”

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

“…Several publications have demonstrated the meconium-inactivating effect on surfactants 7,12,20,[23][24][25] . However, there are a small number of investigations that studied the effects of replacement therapy using exogenous surfactants in animal models with MAS.…”

“…Additionally, ventilation time greater than 30 minutes is associated with a high prevalence of pneumothorax and an elevated mortality in this animal model 28 . Herting et al 25 compared the inhibitory effects of meconium on several types of exogenous surfactants and demonstrated that the several surfactants react in a different way to inhibition by meconium, depending on the apoprotein type and concentration. In our experiment, we used a surfactant that was produced with a Brazilian technology by Instituto Butantan, the effectiveness of which had already been demonstrated for SDR treatment in premature rabbits.…”

Antibacterial Activities of the Cathelicidins Prophenin (Residues 62 to 79) and LL-37 in the Presence of a Lung Surfactant Preparation

“…The size of the bubble is changed periodically between a maximum and a minimum diameter, thereby mimicking the cyclic area compression during respiration in the alveolus. The pressure in the bubble is constantly recorded, and as the diameter at the end point is preset, the surface tension at the minimum bubble size (␥ min ) can be calculated by using the law of Laplace (9). Under physiological circumstances a surface tension close to 0 is needed to prevent alveolar collapse at the end of expiration.…”