The critical concentration of surfactant in fetal lung liquid at birth

Kobayashi, Tsutomu; Shido, Akemi; Nitta, Keiko; Inui, Sachiko; Ganzuka, M.; Robertson, Bengt

doi:10.1016/0034-5687(90)90082-a

Cited by 45 publications

(37 citation statements)

References 22 publications

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“…In all samples the concentration of surfactant was 2.5 45 SURFACTANT INACTIVATION BY MECONIUM mg/mL, which is close to the estimated critical concentration of surfactant in fetal lung liquid at birth (33). Measurements were made at 37°C during 50% cyclic area compression at a rate of 20 per minute.…”

Section: Surface Tension Measurementssupporting

confidence: 53%

Resistance of Different Surfactant Preparations to Inactivation by Meconium

et al. 2001

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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...

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Section: Surface Tension Measurementssupporting

confidence: 53%

Resistance of Different Surfactant Preparations to Inactivation by Meconium

et al. 2001

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“…Our present in vitro data indicate a significant negative impact of Curosurf on bacterial growth at a concentration of 20 mg/mL. This is 6-7 times higher than the "critical concentration" of surfactant phospholipids in the fetal lung fluid at birth but less than one fifth of the estimated phospholipid concentration of the alveolar lining layer in adult animals (32). The phospholipid concentration of airway fluid resulting from instillation of 200 mgkg surfactant lipids in a near-term animal 30 min after birth can be calculated only roughly.…”

Section: Herting Etalmentioning

confidence: 50%

Experimental Neonatal Group B Streptococcal Pneumonia: Effect of a Modified Porcine Surfactant on Bacterial Proliferation in Ventilated Near-Term Rabbits

et al. 1994

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jWe studied bacterial proliferation in relation to surfac-bacterial numbers in both groups ventilated for 5 h, but tant treatment in a model of neonatal group B streptococcal values for surfactant-treated animals (8.96 + 0.38) were (GBS) pneumonia. Surfactant (Curosurf) was isolated from lower than those for animals receiving saline (9.46 + 0.50; pig lungs with a method preserving only polar lipids and p < 0.05). After 5 h, 96% of GBS-infected animals had hydrophobic proteins. Near-term rabbit fetuses were ven-positive blood cultures. Light microscopic examination of tilated in a body plethysmograph system. At 15 min, a the right lung of GBS-infected animals revealed inflammasuspension of GBS strain 090 Ia LD (5 mL/kg, concentra-tory changes that tended to be less prominent in surfactanttion -109/mL) was instilled intratracheally. At 30 min, treated rabbits. We conclude that intratracheal inoculation surfactant (n = 12) or sterile saline (n = 13) was adminis-of near-term rabbits with GBS resulted in a significant tered via the airways (2.5 mL/kg). A control group (n = 12) bacterial proliferation during 5 h of ventilation and that received the same volumes of saline. After 5 h the animals bacterial growth was mitigated by treatment with surfacwere killed, and samples for blood cultures and blood gases tant. (Pediatr Res 36: [784][785][786][787][788][789][790][791] 1994) were taken from the heart. The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates. The results were expressed as Abbreviations mean log,, colony forming units/g lung + SD. Compared CFU, colony forming unit with animals (n = 12) killed immediately after GBS instil-GBS, group B streptococcus lation (8.13 2 0.54), there was a significant increase in RDS, respiratory distress syndrome GBS is a frequently encountered pathogen in the neonatal period (1). Vaginal colonization with GBS is commonly found in pregnant women. Vertical transmission occurs in approximately 40% of deliveries, but only approximately 1% of neonates born to these mothers develop clinical signs of GBS infection (2). If diagnosis and treatment are delayed, the condition has a substantial mortality, especially in premature infants (2). Susceptibility to GBS infections depends on host defense factors (e-g. lack of type-specific opsonizing antibodies) and Received January 26, 1994; accepted June 21, 1994. virulence factors (e-g. polysaccharide capsule) of the infecting microorganism (3-6).Animal models using rabbits, mice, and rats have been used for studies of experimental neonatal GBS infections (7)(8)(9). In these studies, the animals were either infected b y injection (7, 9) o r a bacterial suspension was nebulized via the airways in spontaneously breathing animals (8,9). Our intention was t o develop a model of GBS pneumonia in ventilated newborn rabbits infected b y intratracheal injection of a bacterial suspension.RDS and GBS pneumonia are difficult to differentiate o n clinical grounds (lo), and therefore neonates with ...

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“…We used slightly higher Curosurf concentrations and found, even without addition of PxB, ␥ min Ͻ3 mN/m. Kobayashi et al (20) found concentrations of porcine surfactant, as used in our and the study of Calkovska, as critical to obtain optimal ␥ min Ͻ3 mN/m in the PBS. After addition of 0.3 mg/mL meconium, Curosurf/CaCl 2 was inactivated, whereas 1.3 mg/mL meconium were needed to inactivate Curosurf/CaCl 2 /PxB.…”

Section: Polymyxin B Surfactant and Meconiummentioning

confidence: 99%

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

et al. 2006

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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 (CaCl 2 ) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0 -5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl 2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl 2 /PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl 2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.

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The critical concentration of surfactant in fetal lung liquid at birth

Cited by 45 publications

References 22 publications

Resistance of Different Surfactant Preparations to Inactivation by Meconium

Resistance of Different Surfactant Preparations to Inactivation by Meconium

Experimental Neonatal Group B Streptococcal Pneumonia: Effect of a Modified Porcine Surfactant on Bacterial Proliferation in Ventilated Near-Term Rabbits

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

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