Oxidative Inactivation of Surfactants

Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL₄ surfactant (KL₄). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO⁻) or 0.5 mM hypochlorous acid (OCl⁻), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant > KL₄ > NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p < 0.01) but lower concentration of malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL₄ than in beractant (p < 0.05). Surface area cycling for 24 h with 2 mM ONOO⁻ or 0.5 mM OCl⁻ caused both beractant and KL₄ to increase the proportion of light subtypes from 8–10% to 26–29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74–91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease. Accepted for publication: 8 January 1999     

Inhibitory Effects of Oxyradicals on Surfactant Function: Utilizing in Vitro Fenton Reaction

The inhibitory effects of reactive oxygen species (ROS) on the surface tension-lowering abilities of three surfactants were compared: natural lung surfactant (NLS), KL₄ surfactant containing synthetic peptide resembling the hydrophobic/hydrophilic domains of SP-B in an aqueous dispersion of phospholipids, and Survanta? (SUR) containing SP-B and SP-C. The inhibitory concentrations of Fenton reactants (i.e. 0.65 mM FeCl₂, 0.65 mM EDTA, 30 mM H₂O₂), deduced from dose-response plots of FeCl₂ on minimum surface tension (MST) of SUR, were used to assess the Fenton effect on biophysical properties of various surfactants. Neither H₂O₂ (30 mM) nor FeCl₂ with EDTA (both 0.65 mM) alone affected surfactant function, but when mixed together significantly increased (p < 0.01) the MST of SUR compared with KL₄ (p < 0.05) in a FeCl₂ concentration-dependent manner. This effect on NLS was not significant (p= 0.05) at similar phospholipid concentrations. Also, the range of increases in surface adsorption in mN/m at equilibrium surface tension (EST) was 27–40 for SUR, 36–44 for KL₄, and 24–25 for NLS. We speculate that the presence of SP-A and the catalase content in NLS may have protective effects on inactivation of NLS by ROS. We conclude that the in vitro Fenton effect could be a valuable test system for comparing the inactivation range of surfactants by oxyradicals. Accepted for publication: 20 May 1997     

In vitro conversion of surfactant subtypes is altered in alveolar surfactant isolated from injured lungs.

Pulmonary alveolar surfactant can be separated into different subtypes on the basis of their buoyant densities. These subtypes have been characterized as ultraheavy and heavy forms, which are surface-active, and light forms, which are less surface active. The ratio of these subtypes was altered in an animal model of acute lung injury that contributed to the physiologic abnormalities. We used an in vitro method of surface-area cycling to compare conversion of heavy subtypes isolated from injured and from normal lungs. Lung injury was induced in adult rabbits with a subcutaneous injection of N-nitroso-N-methylurethane (NNMU). Conversion of NNMU-injured heavy subtypes to light subtypes was significantly greater than normal heavy subtype conversion at each time point studied from 60 to 180 min of cycling (p less than 0.01). Surfactant protein A (SP-A) was added to heavy subtypes, with no effect on conversion when 1.5% SP-A was added, but the addition of 4.5, 10.5, and 22.5% caused complete conversion to ultraheavy forms with no cycling. With subsequent cycling, there was greater conversion from ultraheavy to lighter subtypes for normal surfactant material than for NNMU-injured material (p less than 0.05). We conclude that the altered ratio of surfactant subtypes in the alveolar lavage of injured lungs was due to a greater conversion of these subtypes within the alveolar space. Furthermore, SP-A may play an important role in the metabolism of alveolar surfactant both in normal and in injured lungs.     

Influence of Phospholipid Composition on the Properties of Reconstituted Surfactants

The influence of phospholipids on the ultrastructure and metabolism of reconstituted surfactants has not been well defined. The aim of this study was to determine if changes in the phospholipid composition of reconstituted surfactants altered their biophysical properties, ultrastructure, and conversion to light subtype by cycling. We prepared various surfactants containing radiolabeled dipalmitoylphosphatidylcholine ([¹⁴C]DPPC). The addition of phosphatidylglycerol (PG) or dipalmitoylphosphatidic acid (PA) to DPPC increased conversion to light subtype. In contrast, the addition of dipalmitoylphosphatidylglycerol (DPPG) to DPPC markedly reduced conversion to light subtype on cycling. DPPC and DPPC+PG produced large liposomes (∼1,000 nm), whereas DPPC+PA or DPPC+DPPG formed multilamellar membranes. Mixtures of DPPC and PA were highly surface active in vitro, whereas the surface activity of DPPC+DPPG was similar to that of DPPC. In conclusion, the ultrastructure, metabolism, and surface active properties of DPPC+PG mixtures were influenced markedly by alterations in the fatty acid composition or polar head group of PG. Accepted for publication: 10 October 1998     

The influence of pH on surface properties of lung surfactants

Protein-lipid interactions at air-liquid interfaces are dependent on electrostatic charges, cations, anions, distribution of protons, and surface potential, which are influenced by pH changes. All of these factors may affect lung surfactant function. To verify the pH dependence of surface activity of pulmonary surfactant, we studied the in vitro effects of pH and Ca²⁺ on the surface tension-lowering abilities of various surfactants in an oscillating bubble surfactometer. Surface tension measurements were made of mixtures at known pHs or after the replacement of the subphase fluid of surfactant films with buffered saline at various pH values. At the pH range 4.0–7.0, the average equilibrium surface tension (EST)/minimum surface tension (MST) for natural surfactants human amniotic fluid and natural lung surfactant from rabbit lung lavage was 24/2 mN/m. At the same pH range, Exosurf and phospholipids alone had an EST/MST of 44/25 and 44/12 mN/m, respectively. Survanta (SUR) containing SP-B and SP-C and a phospholipid surfactant (KL₄) containing a leucine/lysine peptide had an EST/MST of 29/5 and 36/3, respectively. Alkalinization of the subphase (pH > 7.4) significantly decreased the surface tension-lowering ability of SUR (P < 0.01) and to a lesser extent that of KL₄ surfactant (P < 0.05), but natural lung surfactants were not significantly affected over a pH range of 3–7.5. These data demonstrate that natural surfactants maintain their optimal surface activities over a broader pH range than do the commercial products because of a lack of SP-A. Careful monitoring of the pH for optimal surface activity is recommended when evaluating surfactant function and the effects of specific inhibitors on this function. Offprint requests to: J. D. Antirkhanian, PhD     

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

This article starts with a brief account of the history of research on pulmonary surfactant. We will then discuss the morphological aspects and composition of the pulmonary surfactant system. We describe the hydrophilic surfactant proteins A and D and the hydrophobic surfactant proteins B and C, with focus on the crucial roles of these proteins in the dynamics, metabolism, and functions of pulmonary surfactant. Next we discuss the major disorders of the surfactant system. The final part of the review will be focused on the potentials and complications of surfactant therapy in the treatment of some of these disorders. It is our belief that increased knowledge of the surfactant system and its functions will lead to a more optimal composition of the exogenous surfactants and, perhaps, widen their applicability to treatment of surfactant disorders other than neonatal respiratory distress syndrome. Accepted for publication: 8 July 1996     

Direct and Phagocyte-mediated Lipid Peroxidation of Lung Surfactant by Group B Streptococci

In newborn infants, group B streptococci (GBS) often cause pneumonia, with polymorphonuclear leukocytes (PMN) migrating into the lungs. Because surfactant therapy may be needed in such patients, we evaluated the interaction between GBS or GBS-stimulated PMN and a surfactant preparation (Curosurf) in vitro. The superoxide production of GBS strains or GBS-activated PMN was measured, using the nitroblue tetrazolium (NBT) test and the subsequent lipid peroxidation (LPO) as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The growth of GBS in surfactant was determined and related to the LPO. Finally, the effect of LPO on surfactant activity, caused by GBS-stimulated PMN, was assessed by measuring dynamic surface tension in a pulsating bubble surfactometer. Curosurf diminished the NBT reduction by both live GBS and GBS-stimulated PMN. Surfactant was peroxidized by reactive oxygen species (ROS) from both GBS and GBS-stimulated PMN in a time-dependent manner. Vitamin E significantly reduced the peroxidation level of surfactant in both cases. Surfactant peroxidation was associated with a reduction in the number of live bacteria. The biophysical activity of Curosurf was impaired by GBS-stimulated PMN, as reflected by increased minimum surface tension during cyclic compression. These findings indicate that Curosurf undergoes LPO by ROS produced by GBS and/or PMN. We speculate that exogenous surfactant preparations should be supplemented with vitamin E or another antioxidant, when given to infants with GBS pneumonia. Accepted for publication: 21 August 2000     

Lung Function and Bacterial Proliferation in Experimental Neonatal Pneumonia in Ventilated Rabbits Exposed to Monoclonal Antibody to Surfactant Protein A

Surfactant protein A (SP-A) increases the resistance of surfactant to inhibition by plasma and other proteins. In a previous study we found that a monoclonal anti-SP-A antibody (R 5) increased the sensitivity of surfactant to inhibition by fibrinogen in vivo and in vitro. SP-A has been shown to stimulate microbial phagocytosis and killing by alveolar macrophages. We hypothesized that using R 5 to inactivate SP-A in an animal model mimicking congenital group B streptococcal (GBS) pneumonia might result in increased bacterial proliferation and a deterioration in lung function. Newborn near term rabbits were delivered by Cesarean section, anesthetized, tracheotomized, and ventilated for 5 h in a plethysmograph system allowing measurement of dynamic lung-thorax compliance. Postnatally the animals received one intratracheal injection (5 ml/kg) of R 5, nonspecific IgG, or normal saline. At 30 min all animals received a standard dose of an encapsulated GBS strain by intratracheal injection. The number of bacteria (mean log₁₀ CFU/g lung ± S.D.; CFU = colony forming unit) was evaluated in lung homogenates. Histologic lung sections were judged by light microscopy. Bacterial proliferation was similar in rabbits treated with the monoclonal antibody (9.33 ± 0.39; n= 14) and in control animals receiving saline (9.16 ± 0.35; n= 14) or nonspecific IgG (9.26 ± 0.31; n= 11). No significant differences were noted on the histologic analysis or in measurements of lung function. We conclude that intratracheal instillation of a monoclonal anti-SP-A antibody did not increase bacterial proliferation in GBS-infected newborn rabbits. These findings suggest that SP-A does not play an important role in protection against encapsulated GBS strains in the neonatal period. Accepted for publication: 20 June 1997     

Lipid Peroxidation of Lung Surfactant by Bacteria

The epithelium of the lung is lined with extracellular pulmonary surfactant. This is the surface that invading bacteria first come into contact with when they enter the alveoli. As bacteria become established and interact with this layer, various characteristics of surfactant may become altered. We studied free radical production by three bacterial species, group B streptococci, Escherichia coli, and Pseudomonas aeruginosa, as well as the effect of two concentrations of lung surfactant (Curosurf at 0.04 and 0.4 mg/ml) on this production estimated by the nitro blue tetrazolium reduction test. We also measured the lipid peroxidation of surfactant at various incubation times (0–20 h), using a LPO-586 test kit. In addition, the effect of vitamin E as an antioxidant in a concentration of 0.5 μM was determined by the lipid peroxidation test. We found that the nitro blue tetrazolium reduction by the three bacterial species and lipid peroxidation of lung surfactant increased with time. Vitamin E reduced the lipid peroxidation of this surfactant. By measuring bacterial growth at various incubation times we showed that lung surfactant was bactericidal to group B streptococcal and E. coli strains and that P. aeruginosa strains were resistant to surfactant. We conclude that bacteria, probably by their production of reactive oxygen species, cause lipid peroxidation of lung surfactant. Accepted for publication: 5 October 1998     

Serum Surfactant Protein A Levels in Healthy Individuals Are Increased in Smokers

Serum levels of surfactant protein A (SP-A) were studied in 237 healthy subjects in relation to sex, age, and smoking habits. SP-A values in male smokers were significantly higher than those in male nonsmokers (p < 0.001). The amount of cigarette smoking did not correlate significantly with SP-A values, however. SP-A values in young nonsmoking males and females were somewhat lower than those in older, but without significant difference. No significant difference in values was found between the sexes. We conclude that (1) smoking increases serum levels of SP-A, and (2) SP-A serum levels are not affected by age and sex. Accepted for publication: 6 March 1998     

Inhalation of α1-Protease Inhibitor in Cystic Fibrosis does not affect Surfactant Convertase and Surface Activity

The inhalation of alpha(1)-protease inhibitor (alpha(1)-PI) was assessed in a pilot study to restore the protease-antiprotease balance in the lungs of cystic fibrosis (CF) patients. In addition, the effect of this treatment on the surface active properties of lung surfactant and the metabolic conversion of aggregate forms was studied. Eight young adults with CF inhaled 100 mg of alpha(1)-PI twice daily over 8 weeks and bronchoalveolar lavages (BAL) were obtained before and 12 h after the last inhalation. Large aggregate (LA) forms of surfactant were isolated from the in vivo material by ultracentrifugation and their conversion into small aggregates (SA) was assessed by an in vitro surface area cycling assay. Although alpha(1)-PI partially restored the protease-anti-protease imbalance and reduced BAL protein content, no effects were noted on the impaired minimal surface tension and on the in vivo and in vitro conversion of LA to SA. Antiserum against the specific carboxyl esterase ES-2, previously identified in mice and rats as the putative surfactant convertase, did not detect a protein of the appropriate size in CF BAL. Whereas short-term inhalation of alpha(1)-PI was beneficial for the proteolytic aspects of CF lung injury, this appeared not to be the case for surfactant conversion and surface activity. Copyright Academic Press.     

Lung surfactant components in bronchoalveolar lavage after inhalation of NO2 as markers of altered surfactant metabolism

To study the effects of nitrogen dioxide (NO₂) inhalation on lung lavage surfactant components as markers of an altered surfactant metabolism in type II pneumocytes, rats were exposed to atmospheres with increasing NO₂ concentrations (0.8, 5.0, and 10.0 ppm) over 1 and 3 days. After exposure lung lavage was performed and surfactant components as well as lavagable cells analyzed. An increased number of total lavage cells was found with increasing concentration and duration of NO₂ exposure. Cell distribution showed an elevation in the number of granulocytes and lymphocytes whereas the number of macrophages was, diminished. The amount of total lavage protein revealed an increase related to NO₂ concentration and duration. Also the content of lavage phospholipid was increased, with a decreased portion of phosphatidylcholine (PC). Further analyses of PC showed a diminished composition of saturated fatty acids but an elevated content of the unsaturated portion. Functional studies on surfactant phospholipid extracts exhibited comparable values for the surface tension at equilibrium, as well as for the maximal and minimal surface tension of animals exposed to 0.8 ppm NO₂ and controls. Higher NO₂ concentrations (5 and 10 ppm) resulted in increased values for surface tension compared to controls. This was also observed with purified surfactant that was obtained from controls and from NO₂-exposed rats. These experiments show that in vitro exposure of purified surfactant to NO₂ atmospheres was more effective than exposure in vivo. When the structure of the surfactant proteins A was studied it was found not to be altered by the N0₂. The data clearly demonstrate that NO₂ inhalation impaired function of surfactant components that may be used as markers of altered surfactant metabolism. Offprint requests to: B. Müller     

Effects of Initial Low Flow Reperfusion and Surfactant Administration on the Viability of Perfused Cadaveric Rat Lungs

To expand the cadaveric lung donor pool, protecting the endothelium and alveoli from warm ischemia and reperfusion injury is important. The effects of initial low flow reperfusion and surfactant administration were studied in non–heart-beating donor lungs. The rat heart-lung bloc was excised immediately (group 1) or 30 min (groups 2–4) after euthanasia (n= 6 in each group). The graft was ventilated and reperfused (50 ml/min) immediately after excision for 1 h in groups 1 and 2. In groups 3 and 4, the reperfusion flow rate was increased gradually to 50 ml/min, while ensuring that the pulmonary arterial pressure did not exceed 40 mmHg. Then the graft was reperfused for 1 h. Surfactant was introduced into the airway in group 4 before reperfusion. Airway pressure (AWP) and pulmonary arterial pressure were monitored during reperfusion. After reperfusion, the wet/dry weight ratio (W/D) of the right lung was calculated, and histologic examination using trypan blue staining of the left lung was performed. In group 2, lung failure appeared in all animals during reperfusion. In group 3, although all lungs were reperfused for 1 h, AWP and W/D were higher than in group 1. In group 4, AWP and W/D were lower than in group 3. Histologic examination showed that surfactant administration had attenuated the alveolar cell death. To avoid damage caused by high pulmonary arterial pressure associated with graft reperfusion, iniital low flow reperfusion was beneficial in cadaveric lungs. Surfactant administration before reperfusion was effective in preventing pulmonary edema. Accepted for publication: 16 July 1998     

An examination of the different variables affecting surfactant aggregate conversion in vitro

Pulmonary surfactant exists in 2 major subtypes, the freshly secreted, surface-active large surfactant aggregates (LA) and their metabolic product, the less surface active, small aggregates (SA). Conversion of LA into SA can be studied using an in vitro technique, surface area cycling, which involves the rotation of a suspension of LA end-over-end so that the surface area of the liquid changes twice each cycle. In order to further elucidate the mechanisms involved in aggregate conversion, we have examined the effects of time, temperature, change in surface area, cycling speed, surfactant concentration, and albumin on aggregate conversion in vitro. Three different surfactant preparations were used; rabbit LA, sheep LA, and an exogenous surfactant preparation, bovine lipid extract surfactant (BLES). Based on our results that showed that these variables affected aggregate conversion, we concluded that the adsorption of surfactant at the changing air-liquid interface was an important step in aggregate conversion. However, the results also indicated that aggregate conversion was not solely due to the adsorption characteristics of the surfactant. Other surfactant properties, such as the activity of serine protease or film stability at the air-liquid interface, may also be important in aggregate conversion.     

Developmental Regulation of the Effects of Surfactant Protein A on Phospholipid Uptake by Fetal Rat Type II Pneumocytes

Surfactant protein A (SP-A) enhances the uptake of phospholipid by type II cells derived from adult and late gestation fetal rat lung. The present study was performed to examine more fully the developmental biology of the effects of SP-A on phosphatidylcholine (PC) uptake, to determine the effect of SP-A on the cellular location of bound and internalized phospholipid and on the metabolism of internalized phospholipid by morphologically undifferentiated (18-day) and morphologically differentiated (19-day) fetal type II cells. SP-A enhanced uptake almost twofold in a dose-dependent manner in 19-day fetal cells, but it had no effect on uptake by 18-day fetal cells at any concentration. Stimulation of uptake by 19-day fetal cells was saturable at concentrations above 1 μg/ml SP-A. Maximal uptake was 1.12 nmol of PC/mg of protein, and the effective concentration that yields 50% maximal response, K_Φ, was 58.9 ng/ml (84.1 pM). The effect of SP-A on uptake by 19-day fetal cells was detectable as early as 1 min of exposure. Uptake correlated significantly with time both in the absence (r= 0.98, p < 0.001) and presence of 5 μg/ml SP-A (r= 0.979, p < 0.001). The rate of uptake in the presence of SP-A (0.019 ± 0.002 nmol of PC/mg of protein/min) was twice the rate of uptake in controls (0.009 ± 0.001 nmol of PC/mg of protein/min). SP-A had no effect on binding to plasma membranes and uptake of phospholipid into lamellar bodies by 18-day fetal cells. On the other hand, SP-A significantly enhanced binding of dipalmitoyl phosphatidylcholine to plasma membranes (two- to threefold) and uptake into lamellar bodies (threefold) of 19-day fetal cells. SP-A caused a significant reduction in the degradation of internalized phospholipid by differentiated fetal type II cells. Based on the lack of effect of exogenous SP-A on 18-day fetal cells, we conclude that the response to SP-A is under developmental control. SP-A enhances the initial binding to the plasma membranes of fetal type II cells and subsequent internalization into the lamellar bodies. This effect is associated with a protection of internalized phospholipid from metabolic degradation. Both of these processes are developmentally regulated during the transition from the canalicular to the saccular phase of lung development. Accepted for publication: 15 May 1997     

Photoreduction of Copper Ions Using Silica–Surfactant Hybrid and Titanium (IV) Oxide under Sulfuric Acid Conditions

Photoreduction of Cu²⁺ ions to Cu metal by titanium(IV) oxide (TiO₂) was conducted in the presence of a silica–surfactant hybrid under sulfuric acid conditions. After irradiation, a dark-red color, reflections due to Cu metal in the X-ray diffraction pattern, and peaks due to Cu 2p_1/2 and 2p_3/2 in the X-ray photoelectron spectrum indicated the precipitation of Cu metal in the product. In addition, an increase in the Brunauer–Emmett–Teller specific surface area from 36 and 45 m²/g for the silica–surfactant and TiO₂, respectively, to 591 m²/g for the product, and a decrease in the intensity of the C-H stretching band in the Fourier–transform infra-red spectra implied the removal of surfactant during the reaction. These characteristics were never observed when TiO₂ was used solely. Therefore, this study indicated that the photoreduction of Cu²⁺ ions to Cu metal by TiO₂ was facilitated under the sulfuric acid medium, where the surfactants extracted from silica–surfactant hybrids by protons in the acidic condition were successfully photo-oxidized by TiO₂. Thus, this study presents a new application of the conversion of a silica–surfactant hybrid into mesoporous silicas.     

BAL Surfactant Protein A and Clara Cell 10-kDa Protein Levels in Healthy Subjects

Lung surfactant protein A (SP-A) and Clara cell 10-kDa protein (CC10) are the most abundant proteins produced locally in the lower respiratory tract, as assessed in bronchoalveolar lavage (BAL) analysis. However, it is not known what factors influence SP-A and CC10 levels in BAL fluids, and the relationship between SP-A and CC10 levels in BAL fluids has been unclear. We measured SP-A and CC10 concentrations in BAL fluids from 11 healthy nonsmokers and 12 healthy smokers by enzyme-linked immunosorbent assays using specific antibodies. Mean SP-A and CC10 levels in BAL fluids of healthy smokers were significantly lower than those of healthy nonsmokers. SP-A values correlated significantly with CC10 and phospholipid values in BAL fluids. CC10 values tended to correlate with phospholipid values in BAL fluids. On BAL examinations using three 50-ml aliquots, the mean SP-A level in the second lavage was 2.0-fold and 2.4-fold, respectively, of that in the first and third lavages, and the mean CC10 level in the first lavage was 5.0-fold and 5.6-fold, respectively, of that in the second and third lavages. We conclude that BAL fluid SP-A and CC10 levels are influenced by the BAL methods and by cigarette smoking. There is a significant positive correlation between SP-A and CC10 values in BAL fluids of healthy subjects. Accepted for publication: 3 October 1997     

Diminished Lung Compliance and Elevated Surfactant Lipids and Proteins in Nutritionally Obese Young Rats

Dietary-induced obesity is associated with increases in lung weight, lung volume, alveolar surface area, and number of lamellar bodies in alveolar epithelial type II cells. This suggests that alterations in lung compliance and surfactant content may also occur. The effects of dietary-induced obesity on lung function and surfactant composition were studied in newborn male rats raised in (1) small litters until weaning and then fed a high fat diet (Obese Group, n = 23) and (2) normal-sized litters until weaning and subsequently fed a normal rat diet (Control Group, n = 29). At age 8 weeks, lung function was measured in anesthetized, spontaneously breathing rats, and surfactant composition was analyzed in lung tissue and lavage fluid. The 8-week-old obese rats had a higher body weight (31%) and fat pad weight/body weight ratio (224%) than the Control Group. When compared with control animals, obese rats had an increased respiratory rate, reduced tidal volume, and decreased lung compliance (dynamic and specific). Disaturated phosphatidylcholine (DSPC) in lung tissue and surfactant pellets (large aggregates) and SP-A and SP-B levels in large aggregates were higher in obese than control rats. Phospholipid, DSPC, and triglyceride contents were also elevated in lung tissue in obese rats, suggesting intracellular lipid accumulation, but low relative to alveolar surface area. Thus, alterations in lung function and surfactant lipids and proteins occur in dietary-induced obesity in young rats. We speculate that intrapulmonary lipid deposition and possible surfactant deficiency relative to alveolar surface area may contribute to the reduction in lung compliance in obese rats.     

Surfactant Therapy for Respiratory Distress Syndrome in Premature Neonates

Exogenous surfactant therapy has been part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since the beginning of the 1990s. Discoveries that led to its development as a therapeutic agent span the whole of the 20th century but it was not until 1980 that the first successful use of exogenous surfactant therapy in a human population was reported. Since then, randomized controlled studies demonstrated that surfactant therapy was not only well tolerated but that it significantly reduced both neonatal mortality and pulmonary air leaks; importantly, those surviving neonates were not at greater risk of subsequent neurological impairment.Surfactants may be of animal or synthetic origin. Both types of surfactants have been extensively studied in animal models and in clinical trials to determine the optimum timing, dose size and frequency, route and method of administration. The advantages of one type of surfactant over another are discussed in relation to biophysical properties, animal studies and results of randomized trials in neonatal populations. Animal-derived exogenous surfactants are the treatment of choice at the present time with relatively few adverse effects related largely to changes in oxygenation and heart rate during surfactant administration. The optimum dose of surfactant is usually 100 mg/kg.The use of surfactant with high frequency oscillation and continuous positive pressure modes of respiratory support presents different problems compared with its use with conventional ventilation.The different components of surfactant have important functions that influence its effectiveness both in the primary function of the reduction of surface tension and also in secondary, but nonetheless just as important, role of lung defense. With greater understanding of the individual surfactant components, particularly the surfactant-associated proteins, development of newer synthetic surfactants has been made possible.Despite being an effective therapy for RDS, surfactant has failed to have a significant impact on the incidence of chronic lung disease in survivors. Paradoxically the cost of care has increased as surviving neonates are more immature and consume a greater proportion of neonatal intensive care resources. Despite this, surfactant is considered a cost-effective therapy for RDS compared with other therapeutic interventions in premature infants.     

Tracheal aspirate surface tension in babies with hyaline membrane disease: Effects of synthetic surfactant replacement

Our objective was to determine changes in surface tension of tracheal aspirate over the first 4–5 days of life in babies with hyaline membrane disease, with and without synthetic surfactant replacement. Tracheal aspirates were collected prior to and for 96–108 hr after initiation of a randomized double-blind trial of synthetic surfactant (EXOSURF® Neonatal) or air-treated control patients. Using the captive bubble technique, we measured minimum surface tension (initial adsorption, first quasi-static compression, dynamic cycling at 30 cpm, second quasi-static compression and 5 min after quasi-static compressions) in 39 surfactant-treated and 44 control babies. We also compared minimum surface tension with the respiratory support provided. Twelve hours after one dose of synthetic surfactant, minimum surface tension on first quasi-static compression decreased significantly from 20.9 ± 1.4 to 17.6 ± 1.3 mN/m compared to air-treated babies, who did not show any change. Reduction in minimum tracheal aspirate surface tension on first quasi-static compression and during dynamic cycling over 48–60 hr occurred more rapidly in surfactant-treated babies. Ventilator support did not correlate with minimum tracheal aspirate surface tension. We conclude that treatment of babies with synthetic surfactant improved tracheal aspirate minimum surface tension within 12 hr of the first dose and for the next 48–60 hr. Pediatr Pulmonol. 1998;26:173–182. © 1998 Wiley-Liss, Inc.