Exogenous Surfactant Preparations Research Articles

Role of surfactant in the pathogenesis of bronchopulmonary pathology

Pulmonary surfactant is an important structure of the lungs, providing basic vital functions: reducing alveolar surface tension and facilitating breathing, preventing collapse of the airways and ensuring their patency, protection against infections and pathological environmental factors. Although disturbances of surfactant homeostasis are usually considered in the context of respiratory distress syndrome in preterm infants, it has been established that many lung diseases in adults are accompanied by significant disturbances of surfactant homeostasis. However, preclinical and clinical studies of bronchopulmonary pathology too often overlook the potential role of changes in the qualitative or quantitative composition of pulmonary surfactant in the pathogenesis and development of disease symptoms. In many lung diseases, whether these disturbances in homeostasis are cause or effect remains contravertial field. This review will examine current data on the composition, main functions of pulmonary surfactant and the role of its dysfunction in the pathogenesis of the most frequently encountered bronchopulmonary diseases in the practice of pulmonologists, therapists and rehabilitation specialists, in particular, such as acute respiratory distress syndrome in adults, including associated with a new coronavirus infection, pneumonia of various etiologies and their consequences, bronchial asthma, chronic obstructive pulmonary disease. The review presents the current best practices of replacement therapy with exogenous surfactant preparations and the prospects for pharmacological modulation of surfactant homeostasis disorders in the above nosological forms.

Efficacy of surfactant therapy of ARDS induced by hydrochloric acid aspiration followed by ventilator-induced lung injury - an animal study.

The development of acute respiratory distress syndrome (ARDS) is known to be independently attributable to aspiration-induced lung injury. Mechanical ventilation as a high pressure/volume support to maintain sufficient oxygenation of a patient could initiate ventilator-induced lung injury (VILI) and thus contribute to lung damage. Although these phenomena are rare in the clinic, they could serve as the severe experimental model of alveolar-capillary membrane deterioration. Lung collapse, diffuse inflammation, alveolar epithelial and endothelial damage, leakage of fluid into the alveoli, and subsequent inactivation of pulmonary surfactant, leading to respiratory failure. Therefore, exogenous surfactant could be considered as a therapy to restore lung function in experimental ARDS. This study aimed to investigate the effect of modified porcine surfactant in animal model of severe ARDS (P/F ratio </=13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.25) followed by VILI (V(T) 20 ml/kg). Adult rabbits were divided into three groups: untreated ARDS, model treated with a bolus of poractant alfa (Curosurf®, 2.5 ml/kg, 80 mg phospholipids/ml), and healthy ventilated animals (saline), which were oxygen-ventilated for an additional 4 h. The lung function parameters, histological appearance, degree of lung edema and levels of inflammatory and oxidative markers in plasma were evaluated. Whereas surfactant therapy with poractant alfa improved lung function, attenuated inflammation and lung edema, and partially regenerated significant changes in lung architecture compared to untreated controls. This study indicates a potential of exogenous surfactant preparation in the treatment of experimental ARDS.

Early Immunomodulatory Effects of Different Natural Surfactant Preparations in Preterms With Respiratory Distress.

BackgroundRespiratory distress syndrome (RDS) is the most common respiratory disease in premature infants. Exogenous natural surfactant preparations are used in the treatment of RDS. In recent years, it has become increasingly evident that surfactant plays an immunoregulatory role.ObjectivesThe aim of this study was to evaluate cytokine and chemokine response following three different regimens of natural surfactant treatment in preterm newborns with RDS.MethodsPremature newborns below 32 weeks of gestation who were intubated for RDS and given early surfactant rescue therapy were included in the study. Newborns were randomly divided into three groups and Beractant 100 mg/kg (B-100), Poractant alfa 100 mg/kg (Pα-100) and Poractant alfa 200 mg/kg (Pα-200) were administered intratracheally. Blood samples and transtracheal aspirates (TA) were collected just before and 4–6 h after the surfactant treatment. Total eosinophil count, inducible T Cell alpha chemoattractant (ITaC), macrophage inflammatory protein 3 beta (MIP3b), interleukins (IL) 5, 8, 9, 10, 13, immunoglobulin E (IgE), interferon gamma (IFN-γ), eotaxin and tumor necrosis factor beta-1 (TGF-β1) were measured from blood and tracheal aspirate samples.ResultsA total of 45 infants, 15 in each group, were included in the study. Mean gestational age, birth weight, antenatal, demographic and clinical characteristics of the study groups were similar. IFNγ concentration and eosinophil counts in TA decreased after surfactant replacement in all groups, especially in the infants treated with Pα-100 and Pα-200. Eotaxin, TGF beta and IL-8 concentrations in TA increased significantly in the infants treated with Pα-100 and Pα-200. IL-9 levels in TA decreased in the B-100 group but increased in the Pα-100 and Pα-200 groups. Blood levels of cytokines and chemokines showed significantly decreased levels of ITaC and MIP3b only in the B-100 group, but no significant change was observed in the Pα-100 and Pα-200 groups.ConclusionIn our study, the different immunomodulatory effects of natural surfactant preparations on newborn lung is proven. We found that Poractant α, one of the natural surfactant preparations, shifted the lung immune system toward TH2.

Pulmonary Surfactant: A Unique Biomaterial with Life-saving Therapeutic Applications.

Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, leading to innovative therapeutic avenues for the treatment of several respiratory diseases.

EXOGENOUS SURFACTANTS OF NATURAL ORIGIN IN THE TREATMENT OF RESPIRATORY DISTRESS SYNDROME - COMPARATIVE COMPOSITION, BIOPHYSICAL PROPERTIES AND CLINICAL EFFECTIVENESS

Respiratory distress syndrome (RDS) remains an important cause of morbidity and mortality in premature infants in Ukraine and around the world. Since the determination of surfactant deficiency as the main cause of this disease, significant progress has been made in studying the structure and function of the pulmonary surfactant system, as well as the possibilities of creating and effective use of exogenous surfactant preparations. Unprecedented long-term fundamental, experimental and clinical studies have ensured the clinical availability of numerous exogenous surfactant preparations, the use of which is currently considered one of the standards of neonatal care, regardless of the level of development of the country. However, all these surfactants are not alike. Although all surfactants licensed for clinical practice significantly reduce mortality in preterm infants from RDS, they differ in phospholipid and protein composition, phospholipid concentration, biophysical properties, dosage, possibilities of less invasive administration, applicability, and clinical efficacy. Comparative clinical studies have shown the benefits of poractant-α, which can be administered at a dose that provides more phospholipids in a smaller volume, contains more surfactant-specific proteins (primarily SPB), and is licensed for administration by the less invasive method. The developers of third-generation synthetic surfactants, which have already demonstrated their clinical effectiveness, place their main hopes on the imitation of these properties. This review presents current data on the structure, composition, and biophysical properties of pulmonary surfactant, provides a comparative description of the most commonly used preparations of exogenous surfactant of animal origin, and characterizes additional prerequisites for the effective use of surfactant therapy.

DMBT1 is upregulated in lung epithelial cells after hypoxia and changes surfactant ultrastructure.

Hypoxia and asphyxia are known to induce surfactant inactivation in newborns. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. It was detected in hyaline membranes of infants with respiratory distress syndrome. Human recombinant DMBT1 is able to increase the surface tension of exogenous surfactant preparations in a dose-dependent manner. Immunohistochemistry was performed on lung sections of infants who died due to pre-, peri- or postnatal hypoxia. The lung epithelial cell line A549 was stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty plasmid (DMBT1- cells). The cells were cultured in normoxic or hypoxic conditions, and then DMBT1 as well as HIF-1α RNA expression were analyzed by using real-time-polymerase chain reaction. Human recombinant DMBT1 was added to the modified porcine natural surfactant Curosurf to examine the effect of DMBT1 on surfactant ultrastructure with electron microscopy. DMBT1 expression was upregulated in human lung tissue after fetal/peri-/postnatal hypoxia. In addition, in vitro experiments showed increased DMBT1 RNA expression in A549 cells after hypoxia. HIF-1α was upregulated in both DMBT1+ and DMBT1- cells in response to hypoxia. The addition of human recombinant DMBT1 to Curosurf caused an impaired surfactant ultrastructure. DMBT1 is upregulated in response to hypoxia and there seems to be a link between hypoxia and surfactant inactivation.

Changes of redox reactions in the lung tissue under burn injury and combined application of lyophilized xenographt substrate and exogenous surfactant preparation

&lt;p&gt;Oxidative stress in the body of the experimental animals after burn injury arises and develops on the background&lt;br /&gt;of activation of free radical oxidation and decrease of antioxidant activity and increase of endotoxemia. The combined&lt;br /&gt;use of surfactant preparation and lyophilized xenographt substrate after skin burns lead to a significant decrease of&lt;br /&gt;endotoxemia, inhibition of lipid peroxidation processes and restoring functional activity of antioxidant protection.&lt;/p&gt;

Effects of Two Different Exogenous Surfactant Preparations on Serial Peripheral Perfusion Index and Tissue Carbon Monoxide Measurements in Preterm Infants with Severe Respiratory Distress Syndrome

Administration of an exogenous surfactant may affect both ventilatory and hemodynamic parameters in preterm infants with respiratory distress syndrome (RDS). Peripheral perfusion may be expected to be influenced, and serial perfusion index (PI) values may show this effect. Noninvasive transcutaneous carbon monoxide (TCO) monitoring may show RDS severity, oxidative and inflammatory stress, and response to surfactant treatment. This randomized controlled nonblinded study was performed in 30 preterm infants with RDS, treated with poractant alfa (n = 15) or beractant (n = 15); 18 preterm infants without RDS served as a control group. Oxygenation and hemodynamic parameters were recorded and compared through the first 6 hours of treatment. PI and TCO values were measured prior to (Tp), immediately after (T0), and at 5 minutes (T5), 30 minutes (T30), 60 minutes (T60), and 360 minutes (T360) after the bolus surfactant administration. The mean arterial pressure, oxygenation index, pH, and lactate levels were recorded simultaneously. Both study groups had lower Tp PI and higher Tp TCO levels than controls. Both surfactant preparations improved the PI, TCO, mean arterial pressure, oxygenation index, pH, and lactate levels at the end point of T360. However, the median Tp PI value of 1.3 first decreased to 0.86 at T0 (P < 0.001), and then it increased to 0.99 at T5 (p < 0.001) and to 1.25 at T30 (p = 0.037). The median Tp TCO value of 3 decreased to 2, 1.5, 0, and 0 at T0, T5, T30, and T60, respectively (p < 0.001). PI more quickly recovered to Tp values (30 minutes vs. 60 minutes) and reached the control group values (30 minutes vs. 360 minutes) with beractant compared to that with poractant alfa. TCO recovered to Tp values in both groups at the same time (5 minutes vs. 5 minutes), but reached the control group values more quickly (5 minutes vs. 30 minutes) with poractant alfa than with beractant. Patients with RDS had poor perfusion, and PI improved with both surfactant preparations only following a short decline in the 1(st) minute. The expected improvement of PI occurred earlier in the beractant subgroup. TCO declined in both groups, showing lung improvement and decreased oxidative/inflammatory stress, and it was normalized earlier with poractant alfa.

The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury

BackgroundMechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.MethodsMice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).ResultsFor both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.ConclusionsThe data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

News on neonatal respiratory research

We aimed to assess some of the most recent advances in the pulmonary neonatal medicine. For this purpose we reported on the role of the sustained lung inflation (SLI) procedure in the delivery room, the development of new exogenous surfactant preparations, the effectiveness of nasal high frequency ventilation (nHFV), and the treatment of patent ductusarteriosus (PDA) with paracetamol. Moreover, we discussed the possible future role of nanomedicine and stem cells in the treatment of BPD. Proceedings of the 9 th International Workshop on Neonatology · Cagliari (Italy) · October 23 rd -26 th , 2013 · Learned lessons, changing practice and cutting-edge research

AARC Clinical Practice Guideline. Surfactant Replacement Therapy: 2013

We searched the MEDLINE, CINAHL, and Cochrane Library databases for English-language randomized controlled trials, systematic reviews, and articles investigating surfactant replacement therapy published between January 1990 and July 2012. By inspection of titles, references having no relevance to the clinical practice guideline were eliminated. The update of this clinical practice guideline is based on 253 clinical trials and systematic reviews, and 12 articles investigating surfactant replacement therapy. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation scoring system: 1: Administration of surfactant replacement therapy is strongly recommended in a clinical setting where properly trained personnel and equipment for intubation and resuscitation are readily available. 2: Prophylactic surfactant administration is recommended for neonatal respiratory distress syndrome (RDS) in which surfactant deficiency is suspected. 3: Rescue or therapeutic administration of surfactant after the initiation of mechanical ventilation in infants with clinically confirmed RDS is strongly recommended. 4: A multiple surfactant dose strategy is recommended over a single dose strategy. 5: Natural exogenous surfactant preparations are recommended over laboratory derived synthetic suspensions at this time. 6: We suggest that aerosolized delivery of surfactant not be utilized at this time.

Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: A comparison of natural and synthetic surfactants

Surfactant inactivation results from ischemia/reperfusion injury and plays a major role in the pathogenesis of primary graft dysfunction after clinical lung transplantation. Thus, prophylactic administration of exogenous surfactant preparations before the onset of ischemia/reperfusion has proven to be effective in preserving pulmonary structure and function. Various natural and synthetic surfactant preparations exhibit differences regarding the biochemical composition and biophysical properties. In this study we compared the efficacy of preservation of pulmonary structure and function of the natural surfactant preparations Curosurf and Survanta to that of a synthetic surfactant containing an analog of surfactant protein C (SPC-33) in a rat model of ischemia/reperfusion injury. The oxygenation capacity and peak inspiratory pressure during the reperfusion period were recorded. By applying design-based stereology at the light- and electron-microscopic level, pathologic alterations, including alveolar edema, injury of the blood-air barrier and the intra-alveolar as well as intracellular surfactant pools, were quantified. The best oxygenation and preservation of lung structure was achieved with Curosurf. Survanta treatment was associated with the most severe injury of the blood-air barrier, and SPC-33 demonstrated signs of microatelectasis. The intra-alveolar surfactant pool after Curosurf and SPC-33 was dominated by active surfactant subtypes, whereas Survanta was associated with the highest fraction of inactive surfactant. The intracellular surfactant pool did not show any differences between the treatment groups. Taken together, Curosurf achieved the best structural and functional lung preservation, whereas Survanta was inferior to both Curosurf and SPC-33.

Condensing Effect of Palmitic Acid on DPPC in Mixed Langmuir Monolayers

The interaction between deuterated dipalmitoylphosphatidylcholine (DPPC-d62) and palmitic acid (PA) in mixed Langmuir monolayers is studied using vibrational sum frequency generation (VSFG) spectroscopy. Palmitic acid is an additive in exogenous lung surfactant preparations such as Survanta and Surfaxin. The effect of PA on the chain conformation and orientation of DPPC in the liquid-expanded and condensed phases is explored. A condensing effect of PA on DPPC is observed with VSFG. At 12 mN/m, DPPC-d62 alone is in the liquid-expanded phase. Adding PA increases the conformational ordering of DPPC chains and causes DPPC to transition from the expanded phase into the condensed phase. At 42 mN/m, DPPC-d62 and PA form a mixed structure in the condensed phase. The presence of PA decreases the chain tilt angle of DPPC, increasing the orientational ordering of DPPC chains. At 42 mN/m, there is also evidence from the frequency red shift of the PO2- symmetric stretch that the carboxyl group of PA forms a hydrogen bond with the phosphate group of DPPC in the condensed phase. From this work the effect of PA on DPPC is 2-fold: (1) PA increases the chain ordering of DPPC and promotes the LE and TC phase separation and (2) due to the miscibility between DPPC and PA in the condensed phase, PA decreases the collapse pressure.

Multilayers at the surface of solutions of exogenous lung surfactant: Direct observation by neutron reflection

Pharmacy-grade exogenous lung surfactant preparations of bovine and porcine origin, dispersed in physiological electrolyte solution have been studied. The organization and dynamics at the air/water interface at physiological temperature was analysed by neutron reflection. The results show that a well-defined surface phase is formed, consisting of a multilayer structure of lipid/protein bilayers alternating with aqueous layers, with a repetition period of about 70 Å and correlation depths of 3 to > 25 bilayers, depending on electrolyte composition and time. The experimental surfactant concentration of 0.15% (w/w) is far below that used in therapeutic application of exogenous surfactants and it is therefore likely that similar multilayer structures are also formed at the alveolar surface in the clinical situation during surfactant substitution therapy. Lung surfactant preparations in dry form swell in aqueous solution towards a limit of about 60% (w/w) of water, forming a lamellar liquid-crystalline phase above about 34 °C, which disperses into lamellar bodies at higher water concentrations. The lamellar spacings in the surface multilayers at the air/water interface are smaller than those in the saturated limit even though they are in contact with much greater water concentrations. The surface multilayers are laterally disordered in a way that is consistent with fragments of Lα-phase lamellae. The near surface layers of the multilayer structure have a significant protein content (only SP-B and SP-C are present in the preparations). The results demonstrate that a multilayer structure can be formed in exogenous surfactant even at very low concentrations and indicate that multilayers need to be incorporated into present interpretations of in vitro studies of similar lung surfactant preparations, which are largely based on monolayer models.

Morphological alterations of exogenous surfactant inhibited by meconium can be prevented by dextran

BackgroundSurfactant dysfunction due to inhibition is involved in the pathophysiology of meconium aspiration syndrome. Dextran addition has been shown to reverse exogenous surfactant inactivation by meconium, but the precise mechanisms and the morphological correlate of this effect are yet unknown. Morphological surfactant analysis by transmission electron microscopy (TEM) and stereology allows the differentiation of active (large aggregates = LA) and inactive (small aggregates = SA) subtypes.MethodsTo determine the in vitro effects of meconium and dextran addition on the morphology of a modified porcine natural surfactant (Curosurf), Curosurf samples were either incubated alone or together with meconium or with meconium and dextran, fixed and processed for TEM. Volume fractions of surfactant subtypes [lamellar body-like forms (LBL), multilamellar vesicles (MV), unilamellar vesicles (UV)] were determined stereologically.ResultsAll preparations contained LBL and MV (corresponding to LA) as well as UV (corresponding to SA). The volume fraction of UV increased with addition of meconium and decreased with further addition of dextran. Correspondingly, the UV/(LBL+MV) ratio (resembling the SA/LA ratio) increased when meconium was added and decreased when dextran was added to the surfactant-meconium mixture.ConclusionMeconium causes alterations in the ultrastructural composition of Curosurf that can be visualized and analyzed by TEM and stereology. These alterations resemble an increase in the SA/LA ratio and are paralleled by an increase in minimum surface tension. Dextran prevents these effects and may therefore be a useful additive to exogenous surfactant preparations to preserve their structural and functional integrity, thereby improving their resistance to inactivation.

Different therapeutic perspectives for novel exogenous surfactant preparations*

Department of Pediatrics, Hospital Universitario Austral, Pilar, Argentina The authors have no financial interests to disclose.

Surfactant Therapy for Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in the term infant. Therapy for the disease remains problematic, and newer treatments such as high-frequency ventilation and inhaled nitric oxide are being applied with increasing frequency. There is a significant disturbance of the pulmonary surfactant system in MAS, with a wealth of experimental data indicating that inhibition of surfactant function in the alveolar space is an important element of the pathophysiology of the disease. This inhibition may be mediated by meconium, plasma proteins, haemoglobin and oedema fluid, and, at least in vitro, can be overcome by increasing surfactant phospholipid concentration. These observations have served as the rationale for administration of exogenous surfactant preparations in MAS, initially as standard bolus therapy and, more recently, in association with therapeutic lung lavage. Bolus surfactant therapy in ventilated infants with MAS has been found to improve oxygenation in most studies, although there are a significant proportion of nonresponders and in many cases the effect is transient. Pooled data from randomised controlled trials of surfactant therapy suggest a benefit in terms of a reduction in the requirement for extracorporeal membrane oxygenation (relative risk 0.48 in surfactant-treated infants) but no diminution of air leak or ventilator days. Current evidence would support the use of bolus surfactant therapy on a case by case basis in nurseries with a relatively high mortality associated with MAS, or the lack of availability of other forms of respiratory support such as high-frequency ventilation or nitric oxide. If used, bolus surfactant should be administered as early as practicable to infants who exhibit significant parenchymal disease, at a phospholipid dose of at least 100 mg/kg, rapidly instilled into the trachea. Natural surfactant or a third-generation synthetic surfactant should be used and the dosage repeated every 6 hours until oxygenation has improved. Lung lavage with dilute surfactant has recently emerged as an alternative to bolus therapy in MAS, which has the advantage of removing surfactant inhibitors from the alveolar space in addition to augmenting surfactant phospholipid concentration. Combined animal and human data suggest that lung lavage can remove significant amounts of meconium and alveolar debris, and thereby improve oxygenation and pulmonary mechanics. Arterial oxygen saturation inevitably falls during lavage but has been noted to recover relatively rapidly, even in infants with severe disease. Several randomised controlled trials of surfactant lavage in MAS are underway, and until the results are known, lavage must be considered an unproven and experimental therapy.

Constrained sessile drop as a new configuration to measure low surface tension in lung surfactant systems

Existing methodology for surface tension measurements based on drop shapes suffers from the shortcoming that it is not capable to function at very low surface tension if the liquid dispersion is opaque, such as therapeutic lung surfactants at clinically relevant concentrations. The novel configuration proposed here removes the two big restrictions, i.e., the film leakage problem that is encountered with such methods as the pulsating bubble surfactometer as well as the pendant drop arrangement, and the problem of the opaqueness of the liquid, as in the original captive bubble arrangement. A sharp knife edge is the key design feature in the constrained sessile drop that avoids film leakage at low surface tension. The use of the constrained sessile drop configuration in conjunction with axisymmetric drop shape analysis to measure surface tension allows complete automation of the setup. Dynamic studies with lung surfactant can be performed readily by changing the volume of a sessile drop, and thus the surface area, by means of a motor-driven syringe. To illustrate the validity of using this configuration, experiments were performed using an exogenous lung surfactant preparation, bovine lipid extract surfactant (BLES) at 5.0 mg/ml. A comparison of results obtained for BLES at low concentration between the constrained sessile drop and captive bubble arrangement shows excellent agreement between the two approaches. When the surface area of the BLES film (0.5 mg/ml) was compressed by about the same amount in both systems, the minimum surface tensions attained were identical within the 95% confidence limits.

Lipid peroxidation of lung surfactant in experimental neonatal group B streptococcal pneumonia.

Group B streptococcal (GBS) pneumonia, with neutrophilic granulocytes immigrating into the lungs, may occur in neonates. The incidence is particularly high among preterm infants, who often are treated with exogenous surfactant. We have previously demonstrated in vitro that neutrophils stimulated by GBS cause lipid peroxidation (LPO) and functional impairment of lung surfactant. The present study aimed at evaluating LPO of exogenous lung surfactant (Curosurf) and the protective effect of the natural antioxidant, vitamin E in immature ventilated newborn rabbits with experimental neonatal GBS pneumonia. There was a prominent proliferation of GBS in the lungs of animals treated with surfactant and ventilated for 5 h. GBS-infected rabbits had a higher LPO of lung lavage fluid than non-infected ones. The LPO could be diminished using vitamin E, which, however, did not affect bacterial proliferation. During the 5-h incubation period, mean lung-thorax compliance values were significantly lower in GBS-infected than in noninfected animals. We speculate that addition of vitamin E to exogenous surfactant preparations may improve their resistance to LPO and make them more suitable for treatment of neonates with pneumonia.

A comparative study of exogenous surfactant preparations and tracheal aspirate: interfacial tensiometry and properties of foam films

Surfactant replacement therapy has a vital role in the management of respiratory distress syndrome (RDS). Several techniques and models have been largely used to investigate interfacial physico-chemical properties in vitro and to assist clinical efficiency of exogenous surfactant preparations (ESPs) in vivo. Among them are interfacial tensiometry (Langmuir balance coupled with Wilhelmy plate method for surface tension measurement) and black foam film (BFF) method for measuring the capability of ESPs for bilayer foam film formation. Here, we report some freshly established data from a comparative study of Exosurf, Survanta, Curosurf, Alveofact and clinical samples of tracheal aspirate (TA) of newborns with RDS treated with Curosurf. New observations concerning the properties of foam films of ESPs are also reported and discussed. Measured interfacial physico-chemical parameters prove “better” properties in vitro of the SP-B and -C containing preparations Curosurf and Alveofact. Their properties are similar, Alveofact showing a higher surface tension lowering capacity under dynamic conditions. A comparison with measured interfacial parameters of clinical samples shows that after treatment with Curosurf the phospholipid concentration in tracheal aspirates (367 μg/ml) is higher than the minimum phospholipid concentration for stable black film formation ( C t) of all four ESPs studied, while before treatment this concentration (63 μg/ml) is lower than C t. Values of measured “dynamic” parameters of clinical samples after treatment with Curosurf approach those of the exogenous surfactant preparation itself.