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PubMed2004

Dysfunction of pulmonary surfactant in chronically ventilated premature infants.

Infants of <30 wk gestation often require respiratory support for several weeks and may develop bronchopulmonary dysplasia (BPD), which is associated with long-term pulmonary disability or death in severe cases. To examine the status of surfactant in infants at high risk for BPD, this prospective study analyzed 247 tracheal aspirate samples from 68 infants of 23-30 wk gestation who remained intubated for 7-84 d. Seventy-five percent of the infants had one or more surfactant samples with abnormal function (minimum surface tension 5.1-21.7 mN/m by pulsating bubble surfactometer), which were temporally associated with episodes of infection (p = 0.01) and respiratory deterioration (p = 0.005). Comparing normal and abnormal surfactant samples, there were no differences in amount of surfactant phospholipid, normalized to total protein that was recovered from tracheal aspirate, or in relative content of phosphatidylcholine and phosphatidylglycerol. Contents of surfactant proteins (SP) A, B, and C, measured in the surfactant pellet by immunoassay, were reduced by 50%, 80%, and 72%, respectively, in samples with abnormal surface tension (p < or = 0.001). On multivariable analysis of all samples, SP-B content (r = -0.58, p < 0.0001) and SP-C content (r = -0.32, p < 0.001) were correlated with surfactant function. We conclude that most premature infants requiring continued respiratory support after 7 d of age experience transient episodes of dysfunctional surfactant that are associated with a deficiency of SP-B and SP-C.

Bronchoalveolar Lavage Fluid↗

PubMed2003

Surfactant therapy in neonates with respiratory failure due to haemorrhagic pulmonary oedema.

UNLABELLED: We studied the clinical and biochemical factors associated with surfactant dysfunction and factors affecting the responsiveness to exogenous surfactant among 27 neonates with haemorrhagic pulmonary oedema (HPE). HPE was defined as the presence of a large amount of blood-stained lung effluent and respiratory failure which was difficult to differentiate from respiratory distress syndrome. Among the neonates, 33% had very low birth weight, 96% were preterm, 70% were delivered by caesarean section, and 44% had delivery room intubation. The onset of HPE was at 1.5+/-0.1 h (mean +/- SEM) after birth. In 26 cases, surfactant was administered at 3.0+/-1.3 h after the onset of HPE. The concentrations of surfactant protein A (SP-A), disaturated phosphatidylcholine (DSPC), and albumin in the epithelial lining fluid were determined using the first lung effluent from the patients. The level of inhibitory activity against pulmonary surfactant in the effluent was determined in vitro. Surfactant inhibitory activity was associated with lower birth weight, earlier gestational age, delivery room intubation, earlier onset of HPE, and lower SP-A or DSPC concentration. A good response to exogenous surfactant, which was defined as ventilatory index <0.047 at 1 h after surfactant administration, was seen in 82% of cases, and was associated with lower serum albumin, lower birth weight, and earlier gestational age. Cases with higher DSPC concentration prior to surfactant administration and shorter interval between the onset of HPE and surfactant administration showed an immediate response to surfactant, followed by no increase in ventilatory index for 24 h after surfactant administration. CONCLUSION: exogenous surfactant appeared to be a useful adjunctive therapy for overcoming surfactant inhibition and normalising the respiratory status of infants with haemorraghic pulmonary oedema. Surfactant treatment for this indication awaits further investigations including a randomised controlled study.

Albumins↗

PubMed1994

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.

Animals↗

PubMed2004

Lavage administration of dilute surfactant in a piglet model of meconium aspiration.

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf or Exosurf by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 +/- 54, E-LAVAGE = 280 +/- 57; I-BOLUS = 139 +/- 31; E-BOLUS = 152 +/- 29; C = 119 +/- 73 (mean +/- SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.

Animals↗

PubMed2002

Total extracellular surfactant is increased but abnormal in a rat model of gram-negative bacterial pneumonia.

An in vivo rat model was used to evaluate the effects of Escherichia coli pneumonia on lung function and surfactant in bronchoalveolar lavage (BAL). Total extracellular surfactant was increased in infected rats compared with controls. BAL phospholipid content in infected rats correlated with the severity of alveolar-capillary leak as reflected in lavage protein levels (R(2) = 0.908, P < 0.0001). Western blotting showed that levels of surfactant protein (SP)-A and SP-D in BAL were significantly increased in both large and small aggregate fractions at 2 and 6 h postinstillation of E. coli. SP-B was also increased at these times in the large aggregate fraction of BAL, whereas SP-C levels were increased at 2 h and decreased at 6 h relative to controls. The small-to-large (S/L) aggregate ratio (a marker inversely proportional to surfactant function) was increased in infected rats with >50 mg total BAL protein. There was a significant correlation (R(2) = 0.885, P < 0.0001) between increasing S/L ratio in BAL and pulmonary damage assessed by total protein. Pulmonary volumes, compliance, and oxygen exchange were significantly decreased in infected rats with >50 mg of total BAL protein, consistent with surfactant dysfunction. In vitro surface cycling studies with calf lung surfactant extract suggested that bacterially derived factors may have contributed in part to the surfactant alterations seen in vivo.

Animals↗

PubMed2001

Compositional and functional changes of pulmonary surfactant in a guinea-pig model of chronic asthma.

Recent studies have found that severe surfactant dysfunction occurs during an asthma attack, but the changes in surfactant in a guinea-pig model of chronic asthma have not been studied. We therefore analysed the surfactant recovered from guinea-pigs after repeated inhalation of ovalbumin to see if the surfactant recovered from chronic asthmatic lungs would be intrinsically altered. Guinea pigs immunized through repeated inhalation of aerosolized ovalbumin (OA) were exposed to the antigen once a week for a month. Twenty-four hours after the last challenge the alveolar wash was recovered. We calculated saturated phosphatidylcholine (Sat-PC) and total protein (TP) pool sizes in alveolar spaces. Surfactant subtype conversion of large aggregate surfactant (LA) to small aggregate surfactant was studied in vitro by means of the surface area cycling technique. The phospholipid composition of LA was analysed by thin layer chromatography and the surface activity of LA was also determined. We found decreased surfactant pool sizes, decreased ratio of Sat-PC to TP in alveolar lavages in asthma groups, and surface activity of the surfactant recovered from asthmatic lungs to be inferior to that of the controls. Accelerated surfactant subtype conversion in vitro was also noted in the lungs of asthmatic animal models. In addition, the changes in phospholipid compositions which were similar to the pattern of acute lung injury suggested that alveolar inflammation might be involved in the pathogenesis of chronic asthma. These results indicate that surfactant is intrinsically abnormal in chronically asthmatic lungs.

Analysis of Variance↗

PubMed1994

In vivo function of surfactants containing phosphatidylcholine analogs.

Increased phospholipase A2 activity demonstrated in some forms of lung injury may contribute to surfactant dysfunction. Phospholipase A2-resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant properties might therefore be useful lipid components of treatment surfactants for certain lung injuries. The in vivo function of surfactants containing DPPC or the phospholipase-resistant analogs dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine (DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus evaluated in preterm rabbits (27 days' gestation). Rabbits randomly received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C, DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl (control) and were ventilated for 30 min. Lipid-only surfactants decreased ventilatory pressures (peak inspiratory pressures minus positive end-expiratory pressure) relative to control (p < 0.05). Addition of SP-B+C further decreased ventilatory pressures to levels similar to LES (p < 0.01 versus control, lipid-only surfactants). Lung dynamic compliances and postventilation pressure-volume curves improved in the following order: LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p < 0.05). All surfactant preparations decreased intravascular 125I-albumin recoveries in the lungs relative to control (p < 0.01 for all surfactants versus control). These results indicate that DEPC and DEPnC were as effective as DPPC as lipid components of synthetic surfactants. And like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo function to levels comparable to LES.

Animals↗

PubMed1996

Physiologic response and lung distribution of lavage versus bolus Exosurf in piglets with acute lung injury.

Despite evidence of surfactant dysfunction in the acute respiratory distress syndrome (ARDS), treatment with exogenous surfactant remains experimental. Uneven pulmonary distribution is one factor that may limit response. We investigated whether exogenous surfactant administered by lavage, consisting of a 35 ml/kg volume instilled by gravity and followed immediately by passive drainage (LAVAGE), would result in better lung distribution and physiologic response than with surfactant administered as a 5 ml/kg bolus (BOLUS). Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets. In the LAVAGE group (n= 9), 10.1 +/- 0.4 ml/kg of surfactant was retained, corresponding to a phospholipid dose of 136 +/- 5 mg/kg. In the BOLUS group (n = 9), the dose administered was 203 mg/kg phospholipid. Piglets in the LAVAGE group demonstrated greater improvement in pulmonary function, including PaO2, PaCO2, ventilation efficiency index, functional residual capacity (FRC), and pressure-volume curves than piglets in the BOLUS group. Some differences were found in lung distribution of surfactant. We conclude that Exosurf is more effective when administered by lavage in this lung injury model. We speculate that the lavage method of administration holds promise as an alternative method of surfactant administration in patients with ARDS.

Acute Disease↗

PubMedDate not supplied

Current strategy for management of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is characterized by the atelectasis due to the complete airway obstruction, emphysema and air leak syndrome resulted from the partial obstruction of airway, chemical pneumonitis, and surfactant dysfunction. As far as meconium is present in the airway, exogenous surfactant will be inactivated rather quickly even given as multiple doses. MAS can easily develop persistent pulmonary hypertension of the newborn. Therefore, the removal of meconium from the airway rather than the surfactant replacement therapy should be the cardinal step for the treatment of MAS. Our previous studies revealed that the removal of meconium from airway by the tracheobronchial lavage with diluted surfactant solution, 100 mg/10 mL/Kg of Surfactant-TA, resulted in the recovery of both blood gas values and lung compliance to the normal range. Thus, the current strategies of management of MAS are the selective intubation with toileting only on infants with severe distress at birth, and the early airway lavage with diluted surfactant solution, followed by high frequency oscillatory ventilation, which may prevent the further injuries in the fragile neonatal lung.

Female↗

PubMed2004

Surfactant lavage with lidocaine improves pulmonary function in piglets after HCl-induced acute lung injury.

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. The pathophysiology of ARDS includes abnormalities of surfactant function as well as pulmonary inflammation. Immunomodulating drugs, like Lidocaine, have shown some success in decreasing inflammation in ARDS. We attempted to combine surfactant lavage's ability to reverse the surfactant dysfunction, while acting as a vehicle to deliver Lidocaine. Gravity-driven surfactant (Infasurf) lavage (35 ml/kg) was administered alone or mixed with Lidocaine after severe HCl acid injury (0.3 N; 3 cc/kg) in neonatal piglets. Treatment groups included: control (C) ( n = 5), surfactant lavage (SL) (35 ml/kg-diluted Infasurf) ( n = 7) and SL mixed with Lidocaine (SL+L) ( n = 7). About 26-27% of the lavage was retained (phospholipid 73-74 mg/kg; Lidocaine 1.8 mg/kg). Oxygenation progressively increased in the SL and SL+L groups over the 4-hour period (at 240 min: C = 99 +/- 14; SL = 154 +/- 39; SL+L = 230 +/- 40 mmHg) ( p < 0.05). PaCO(2) increased in all groups from 43 +/- 0.3 to 55 +/- 0.7 mmHg. Only SL+L showed a reduction in PaCO(2) (at 240 min: C = 54 +/- 4; SL = 53 +/- 7; SL+L = 49 +/- 2 mmHg) ( p < 0.05). Finally, SL and SL + L had superior characteristics during the quasi-static pressure volume (PV) procedure as compared to Control ( p < 0.05). In our HCl ALI model, SL improved oxygenation and quasi-static lung compliance over C. The pulmonary function effects of SL were further enhanced by the addition of Lidocaine to the surfactant suspension. Combining therapeutic agents with surfactant lavage may be an effective strategy in ALI.

Adjuvants, Immunologic↗

PubMed1997

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant.

UNLABELLED: Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. CONCLUSION: Surfactant therapy normalizes the surfactant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients.

Albumins↗

PubMed1999

Damage to surfactant-specific protein in acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) develops in association with many serious medical disorders. Mortality is at least 40%, and there is no specific therapy. A massive influx of activated neutrophils, which damage pulmonary vascular endothelium and alveolar epithelium, leads to alveolar oedema and pulmonary surfactant dysfunction. In-vitro studies show that neutrophil elastase can cleave surfactant-specific proteins and impair surfactant function. If this happens in vivo in ARDS, the response to surfactant therapy will be limited. METHODS: Samples of pulmonary surfactant were obtained from the lungs of 18 patients with ARDS and six healthy controls by bronchoalveolar lavage. We separated proteins in these samples according to molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). We then used western blotting with monoclonal antibody E8 to detect the major surfactant-specific protein A (SP-A). FINDINGS: By contrast with controls, 14 of 18 patients had evidence of in-vivo damage to SP-A that resembled damage caused to SP-A when it is cleaved by neutrophil elastase. Controls showed a single band of normal dimers at 66 kDa, whereas 14 of 18 patients showed multiple bands at 66 kDa, 55 kDA, and 30-36 kDa, and six showed additional bands at 36-40 kDa. INTERPRETATION: Direct damage to surfactant-specific proteins occurs in lungs of patients with ARDS, probably by proteolysis. Trials of protein-containing therapeutic surfactant are in progress in ARDS, and our results indicate that the frequent failure to maintain response may result from continuing damage to surfactant by products of activated neutrophils. A combination of surfactant and antiprotease therapy may improve therapeutic prospects.

Adolescent↗

PubMed2000

Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism.

Adult respiratory distress syndrome may incorporate in its pathogenesis the hyperplastic proliferation of alveolar epithelial type II cells and derangement in synthesis of pulmonary surfactant. Previous studies have demonstrated that hepatocyte growth factor (HGF) in the presence of serum is a potential mitogen for adult type II cells (R. J. Panos, J. S. Rubin, S. A. Aaronson, and R. J. Mason. J. Clin. Invest. 92: 969-977, 1993) and that it is produced by fetal mesenchymal lung cells (J. S. Rubin, A. M.-L. Chan, D. P. Botarro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfield, J. Wong, T. Miki, P. W. Finch, and S. A. Aaronson. Proc. Natl. Acad. Sci. USA 88: 415-419, 1991). In these studies, we expand on this possible involvement of HGF in chronic lung injury by showing the following. First, normal adult lung fibroblasts transcribe only small amounts of HGF mRNA, but the steady-state levels of this message rise substantially in lung fibroblasts obtained from animals exposed to oxidative stress. Second, inflammatory cytokines produced early in the injury stimulate the transcription of HGF in isolated fibroblasts, providing a plausible mechanism for the increased amounts of HGF seen in vivo. Third, HGF is capable of significantly inhibiting the synthesis and secretion of the phosphatidylcholines of pulmonary surfactant. Fourth, HGF inhibits the rate-limiting enzyme in de novo phosphatidylcholine synthesis, CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15). Our data indicate that fibroblast-derived HGF could be partially responsible for the changes in surfactant dysfunction seen in adult respiratory distress syndrome, including the decreases seen in surfactant phosphatidylcholines.

Animals↗

PubMed1996

Exogenous surfactants in a piglet model of acute respiratory distress syndrome.

Evidence for surfactant dysfunction in acute respiratory distress syndrome (ARDS) suggests a role for exogenous surfactant which contains apoprotein for resistance to protein inhibition. We compared the effects of KL-4-Surfactant, an artificial preparation containing a synthetic 21 amino acid peptide with SP-B-like activity, with Exosurf, an artificial protein-free surfactant, and Survanta, a bovine protein-containing surfactant, in a saline lung lavage model of ARDS in neonatal piglets. Two sequential series of lung lavages were performed to lower PaO2 < 100 mm Hg, each followed by administration of surfactant or air and a 90-min observation period. Progressive lung injury was demonstrated by deterioration in pulmonary function, increasing bronchoalveolar lavage protein, and changes in histopathology. All surfactants improved oxygenation, although oxygenation was generally better with Survanta and KL-4-Surfactant. Further, Survanta and KL-4-Surfactant groups showed improvement in ventilation, with decreases in PaCO2 and increases in FRC. Only KL-4-Surfactant demonstrated greater pressure-volume characteristics and lower bronchoalveolar protein than those of Controls. We conclude that the physiologic effects of KL-4-Surfactant are more like Survanta in this model. We speculate that KL-4-Surfactant may improve pulmonary function, reduce alveolar protein leak, and thus be efficacious in the treatment of ARDS.

Animals↗

PubMed2003

Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma.

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant. Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period. Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0-2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and 23.98% in the PT and the NT group, respectively. The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1995

Pathophysiology of congenital diaphragmatic hernia. XII: Amniotic fluid lecithin/sphingomyelin ratio and phosphatidylglycerol concentrations do not predict surfactant status in congenital diaphragmatic hernia.

Abnormal development of the lung in congenital diaphragmatic hernia (CDH) results in a dysfunctional surfactant system. In premature newborns at risk for respiratory distress syndrome, amniotic fluid lecithin/sphingomyelin (L/S) ratios and phosphatidylglycerol (PG) status have been successfully used to predict the surfactant status in the fetus. The objective of this study was to assess the accuracy of L/S ratios and PG in predicting the surfactant status in CDH. The surgically created lamb CDH model was used. Animals were delivered at 140 days' gestation (term 145) and immediately killed. Before delivery amniotic fluid was collected and L/S ratios and PG status were measured. Bronchoalveolar lavage (BAL) was performed and analyzed for total phospholipid and percent phosphatidylcholine (PC). Analysis of the BAL showed that the CDH lungs had both significantly less total phospholipid (CDH 0.10 +/- 0.03 mg/g versus control (CON) 0.76 +/- 0.28 mg/g) and PC (CDH 38 +/- 7.3% versus CON 70 +/- 3.4%) when compared with controls. In contrast the L/S ratios (CDH 2.44 +/- 0.26 versus CON 2.01 +/- 0.32) and PG status (CDH 8.75 +/- 1.01 nmol versus CON 10.2 +/- 0.9) were the same in CDH and control animals. The BAL from the CDH lamb model has a significant surfactant deficiency. Amniotic fluid L/S ratios and PG status were, however, not different between the control and CDH lambs. These results indicate that amniotic fluid L/S ratios and PG do not accurately predict the surfactant status of a fetus with CDH.

Amniotic Fluid↗

PubMed2002

Effects of simultaneous exposure of surfactant to serum proteins and free radicals.

Free radicals (FRs) and serum proteins have both been implicated in the pathophysiology of surfactant dysfunction during acute lung injury (ALI). This study examines how these 2 distinct mechanisms interact to contribute to altered surfactant function in this setting. Calf lung surfactant (2 mg/mL) was incubated with no additives (C = control), and with low = (LD = 125 microM FeCl2; 250 microM H2O2) and high-dose (HD = 250 microM FeCl2, 500 microM H2O2) Fenton reaction reagents to generate hydroxyl radical. Each condition was studied with (1) no protein (N); and with 25%, 200%, and 800% (weight protein/weight phospholipid) protein added as (2) bovine albumin, (3) bovine fibrinogen, (4) hemoglobin, or (5) calf serum. Lipid (LFR) and protein (PFR) free-radical products, and modifications in the tertiary structure of Surfactant Protein A (SPA) on Western blot, were observed in N LD and N HD samples. Added proteins reduced LFR and PFR changes as well as SPA structural changes. Protection was greatest for fibrinogen, hemoglobin, and serum, and least for albumin. Minimal to no dysfunction, assayed by pulsating surfactometry, was observed in all samples. These findings indicate that addition of serum proteins to surfactant at 2 mg/mL protects against, rather than promotes, FR-mediated chemical changes in surfactant lipid and protein constituents.

Animals↗

PubMed1995

Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry.

Prolonged exposure to O2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2 exposure in primates. Sixteen healthy male baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O2 (n = 6) or 100% O2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group of animals (n = 5) was ventilated with an inspired fraction of O2 of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (VA/Q) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently raised to 10 cmH2O for 30 min to obtain additional measurements of VA/Q. After the experiments, lungs were obtained for biochemical and histological assessment of injury. O2 exposures altered hemodynamics, progressively worsened VA/Q, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O2 toxicity in baboons.

Animals↗