Bovine Surfactant Research Articles

Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.

We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. After confirmation of similar responses to exogenous surfactant, animals were then randomized to one of four ventilation groups; (1) Normal tidal volume (VT) (5 cm H2O): VT = 10 ml/kg, respiratory rate (RR) = 30/min, positive end-expiratory pressure (PEEP) = 5 cm H2O; (2) Normal VT (9 cm H2O): VT = 10 ml/kg, RR = 30/min, PEEP = 9 cm H2O; (3) Low VT (5 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 5 cm H2O; (4) Low VT (9 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 9 cm H2O. Animals were ventilated for an additional 3 h and then killed, and lung lavage fluid was analyzed. Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.

Exogenous surfactant therapy for neonatal respiratory distress syndrome: a two-year clinical experience.

The purpose of this study were to gain local experience, to find out the efficacy and side effects of surfactant and to find out whether surfactant therapy will lower the mortality and morbidity of premature infants. From Nov. 1992 to Dec. 1994, there were 25 premature infants in his neonatal intensive care unit (NICU) enrolled in this study. Another 25 premature infants with study group matched gestational age, weight, and Apgar score, who had been previously treated at this NICU from 1990 to 1992 served as control group. Modified bovine surfactant (Survanta, Abbot), 100 mg/Kg of surfactant phospholipid in 4 ml solution was administered intratracheally in four divided doses. The premature infants in the study group had prompt and sustained improvement in oxygenation. The improvement in FiO2 and arterial-to-alveolar oxygen tension ratio (a/APO2) were significantly different from the control infants from 12 hours post-treatment till the subsequent 48 hours after treatment. There was no difference in mortality rate between the two groups. There was no side effect noted from surfactant therapy. It was therefore concluded that modified bovine surfactant therapy is safe and effective for neonates with respiratory distress syndrome. A larger study is required to find out whether it lowers the mortality and morbidity in premature infants in Taiwan.

Surfactant modifies the lymphoproliferative activity of macrophages in hypersensitivity pneumonitis.

Alveolar macrophages (AM) from normal individuals suppress mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation, whereas cells from patients with hypersensitivity pneumonitis (HP) enhance PBMC. Because surfactant components can interfere with AM functions, we tested the effect of Survanta (a modified bovine surfactant) and surfactant fractions isolated from bronchoalveolar lavage of normal subjects and HP patients on AM-induced lymphoproliferation. Surfactant fractions were isolated from bronchoalveolar lavage fluids by differential centrifugation into total aggregates (TA) and large aggregates (LA). Surfactant preparations (200 micrograms/ml) from 10 normal subjects (N) or 12 HP patients or of Survanta were added to AM-PBMC cocultures stimulated with phytohemagglutinin (PHA) at 1:1 and 2:1 ratios. Results, expressed as percent of PHA-induced PBMC proliferation cocultures without surfactant, show that normal surfactant and Survanta decrease mitogen-induced proliferation of cells to a larger extent than surfactant from HP patients. For AM-to-PBMC ratios of 1:1, the results were as follows: N TA 10.58 +/- 2.75% (mean +/- SE), N LA 12.96 +/- 2.78%, HP TA 43.09 +/- 7.81%, HP LA 61.64 +/- 7.77%, and Survanta 16.70 +/- 2.95%. Similar data were obtained in 2:1 cocultures. Because surfactant components interact with AM, alterations of surfactant composition in lymphocytic diseases, mainly in the LA fraction, may account for the lack of suppressive activity in AM of HP patients and the observed alveolitis.

Administration of Surfactant via Flexible Bronchoscopy

Abstract: Surfactant depletion and dysfunction are significant lesions in the pathogenesis of adult respiratory distress syndrome (ARDS). Some investigators have suggested surfactant replacement as a therapy for ARDS. We have replaced surfactant using flexible bronchoscopy in three patients with severe ARDS. Bovine surfactant (Survanta®, Ross Laboratories, Columbus, OH) at a total dose of 4 ml/kg was administered to each subsegment after the wedge position was established. There were no complications and each procedure was completed in less than 20 minutes.

Acute Hemodynamic Effects of Porcine and Bovine Surfactant Replacement in Surfactant Depleted Newborn Piglets

Background: We have previously shown that instillation of 200mg/kg of porcine surfactant (Curosurf™) induces a systemic vasodilation in surfactant depleted newborn piglets. In the present work we wanted to study if this effect is dependent on dose and further could be induced also by instillation of a bovine surfactant preparation(Survanta™).

Modified Bovine Surfactant Preparations in the Rat Lung Lavage Model

Background: In order to improve biological activity of natural bovine surfactant, we supplemented a commercially available preparation (SF-RII, Alveofact®) with different lipids resp. proteins .Materials and methods: SF-RII was supplemented with 11% phosphatidylglycerol (prep.1), 13% sphingomyelin (prep.2), 7.5% phosphatidylethanolamin-plasmalogen (prep.3), 7% phosphoethanolamin (prep.4) and 2% SP-B (prep.5). These surfactants were tested in the rat lung lavage model: animals were tracheotomized and mechanically ventilated (Babylog 1. Dragerwerk AG. FRG) at a rate of 36/minute, 26/6 cm H2O pressure, FiO2 1.0; surfactant depletion was induced by saline lung lavage until paO2 was < 100 mmHg. SF-RII 100 mg/kg b.w. was given intratracheally and compared with identical doses of the modified surfactant preparations(identical volumes) in 6 animals each with respect to oxygenation .Results: The table gives an overview:

In vivo determination of surface tension in the horse trachea and in vitro model studies

We measured the surface tension in the trachea of the non-anaesthetised horse from the spreading behaviour of fluid drops, using videotracheoscopy. To do this, we placed small oil drops onto the tracheal wall with a thin Teflon tubing inserted into a videocolonoscope used in humans. Either 5 ml of saline (control) or 5 ml of bovine lipid extract surfactant (BLES) at 4 mg/ml were administered. Tracheal surface tension was 31.9±0.54 mN/m (Mean±SEM, n=30) in the control experiments and 24.5±0.51 mN/m (Mean±SEM, n=21) in the entire trachea after the administration of BLES. These values were determined from calibration curves relating film surface tension to the relative diameter of test fluid droplets. In the calibration experiments, the test fluid droplets were placed onto a surfactant film at various surface tensions in either a modified Langmuir–Wilhelmy balance or a captive bubble surfactometer. The spreading behaviour of a given test fluid droplet in the model studies did not only depend on the film surface tension but also on the thickness of the aqueous layer below the surfactant film. Hence, the computed surface tensions in the trachea depend on the choice of which in vitro model is applied.

Cerebral Hemodynamics and Oxygenation Following Surfactant Treatment in Preterm Infants: Comparison Between Two Different Doses. • 978

Introduction Contrasting evidences exist regarding the possible effects of surfactant administration on cerebral perfusion. Aim of this study was to compare changes in cerebral hemodynamics and oxygenation following a 100 mg/kg and 50 mg/kg dose of bovine surfactant.

MODIFIED BOVINE SURFACTANT PREPARATIONS IN THE RAT LUNG LAVAGE MODEL 1507

Background: In order to improve biological activity of natural bovine surfactant, we supplemented a commercially available preparation (SF-RII, Alveofact®) with different lipids resp. proteins .Materials and methods: SF-RII was supplemented with 11% phosphatidylglycerol (prep.1), 13% sphingomyelin (prep.2), 7.5% phosphatidylethanolamin-plasmalogen (prep.3), 7% phosphoethanolamin (prep.4) and 2% SP-B (prep.5). These surfactants were tested in the rat lung lavage model: animals were tracheotomized and mechanically ventilated (Babylog 1. Dragerwerk AG. FRG) at a rate of 36/minute, 26/6 cm H2O pressure, FiO2 1.0; surfactant depletion was induced by saline lung lavage until paO2 was < 100 mmHg. SF-RII 100 mg/kg b.w. was given intratracheally and compared with identical doses of the modified surfactant preparations(identical volumes) in 6 animals each with respect to oxygenation .Results: The table gives an overview:

Mitigation of injury in canine lung grafts by exogenous surfactant therapy

Background: Exogenous surfactant therapy of lung donors improves the preservation of normal canine grafts. The current study was designed to determine whether exogenous surfactant can mitigate the damage in lung grafts induced by mechanical ventilation before procurement. Methods and results: Five donor dogs were subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This produced a significant decrease in oxygen tension ( p = 0.007) and significant increases in bronchoscopic lavage fluid neutrophil count ( p = 0.05), protein concentration ( p = 0.002), and the ratio of poorly functioning small surfactant aggregates to superiorly functioning large aggregates ( p = 0.02). Five other animals given instilled bovine lipid extract surfactant and undergoing mechanical ventilation in the same manner demonstrated no significant change in oxygen tension values, lavage fluid protein concentration, or the ratio of small to large aggregates. All 10 lung grafts were then stored for 17 hours at 4° C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 ± 63 mm Hg in lung grafts administered surfactant versus 73 ± 14 mm Hg in untreated grafts ( p = 0.007). Furthermore, peak inspired pressure was significantly ( p < 0.05) lower in treated animals from 90 to 360 minutes of reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion revealed small to large aggregate ratios of 0.17 ± 0.04 and 0.77 ± 0.17 in treated versus untreated grafts, respectively ( p = 0.009). Conclusions: Instillation of surfactant before mechanical ventilation reduced protein leak, maintained a low surfactant small to large aggregate ratio, and prevented a decrease of oxygen tension in donor animals. After transplantation, surfactant-treated grafts had superior oxygen tension values and a higher proportion of superiorly functioning surfactant aggregate forms in the air space than untreated grafts. Exogenous surfactant therapy can protect lung grafts from ventilation-induced injury and may offer a promising means to expand the donor pool. (J Thorac Cardiovasc Surg 1997;113:342-53)

Exogenous surfactant enhances the delivery of recombinant adenoviral vectors to the lung.

Somatic gene therapy for pulmonary diseases must be accomplished in vivo, requiring the spread of a gene transfer vector across a vast expanse of respiratory epithelium. Surfactant, a naturally occurring protein and lipid mixture used to treat the respiratory distress syndrome of prematurity, disperses rapidly and evenly throughout the lung. We employed exogenous bovine surfactant (Survanta beractant) as a carrier vehicle for pulmonary delivery of a recombinant adenovirus expressing beta-galactosidase (beta-Gal). Rats treated with an adenovirus-beractant mixture demonstrated more uniform lobar distribution of transgene expression than rats treated with the same amount of virus in saline. Tissue homogenates were examined for quantitative beta-Gal expression by reaction with o-nitrophenol beta-n-galactopyranoside (ONPG). The degree of beta-Gal activity was affected by both the volume and type of carrier used to deliver the virus. At low volumes (0.5 ml, 1.3 ml/kg), beractant-treated animals demonstrated significantly greater pulmonary beta-Gal activity than saline-treated animals (p < 0.002) and untreated controls. At high volume (1.2 ml, 4 ml/kg), average beta-Gal activity was similar between groups treated with beractant or saline, but was more variable within the saline treated group. Higher volumes of delivery medium were associated with increased levels of beta-Gal expression regardless of the carrier used. Survanta was well tolerated by the animals and did not affect the duration of transgene expression. Exogenous beractant provides a useful medium for delivering recombinant adenoviruses to the lung when diffuse distribution of transgene expression is desired.

Influence of Blood Constituents on Uptake of a Lipid-Extracted Natural Surfactant by Alveolar Type II Cells

During lung injury, blood constituents may leak into the alveolar space and impair surfactant function. This study investigated possible interferences with the alveolar surfactant life cycle, by assessing the effects of various blood constituents on size, state of aggregation, and uptake of a natural, lipid-extracted bovine surfactant preparation (Alveofact) into isolated rat type II cells in primary culture. The results showed that plasma, serum, albumin, immunoglobulin G, bilirubin, and galactose inhibited uptake according to concentration. Fibrinogen and transferrin enhanced uptake; hemoglobin, fibronectin, and, vitronectin had no effect. Uptake was also impaired when the blood constituents were washed off and the surfactant was added afterward. For some of the blood constituents, a direct interaction with the surfactant liposomes was observed, resulting in changes of liposome size and state of aggregation. However, no correlation between these changes and effects on uptake were found. During lung injury with increased permeability edema, a direct inhibition of surfactant lipid uptake by blood constituents might lead to a reduced delivery of surfactant components into type II cells and disturb surfactant metabolism.

Treatment of neonatal respiratory distress syndrome with Alveofact--results of a prospective observational study

After registration of the bovine Surfactant Alveofact (Fa. Thomae) for treatment of neonatal respiratory distress syndrome (RDS) an observational study was performed in 47 german neonatal departments to register indication, effectivity, mode of administration and unexpected side effects. 680 ventilated preterm infants (gestational weeks 29.5 +/- 2.9; birth weight 1359 +/- 507 g) were enrolled in an uncontrolled clinical study with study-protocol, prospectively defined outcomes and covariates, manual of operation, central control system, biometrical control. Surfactant was applicated at a postnatal age of 2 hours 56 minutes (median). Only 2.9% of newborn infants got the first surfactant doses < 6 min postnatally, 19.4% between 6 ... 60 min and 77.7% > 60 min postnatally. Following 1338 instillations in 76% an improved lung function, in 21% no change and in 3% a worsening was observed. During the study the total dose of surfactant increased. Safety considerations determined by the rate of pulmonary and extrapulmonary complications were similar to data of the literature: pneumothorax 12%, pulmonary interstitial emphysema 11.6%, secondary pneumonia 20.4%, broncho-pulmonary dysplasia 27%, pulmonary hemorrhage 2.1%, peri/intraventricular hemorrhage (degree III/IV) 27.9%, ductus arteriosus persistens 24.4%, sepsis/meningitis 12.4%. During the study the mortality reduces from 31% (first period) to 18% (third period) the mean was 20%. In 44 infants (6.5%) a disturbed ventilation (airway obstruction, overdystension of pulmonary areas, atelectasis) after surfactant administration was observed. In RDS the surfactant Alveofact is preferably used therapeutically (rescue mode), it is effective but not free of risk. Its administration needs for a clear indication. New unknown side effects of Alveofact were not observed.

Acylation of Pulmonary Surfactant Protein-C Is Required for Its Optimal Surface Active Interactions with Phospholipids

This study investigates the importance of thioester-linked acyl groups in lung surfactant protein C (SP-C) in facilitating interactions with phospholipids that yield functionally important surface active behaviors. Native SP-C, palmitoylated at cysteine residues at positions 5 and 6, was isolated from bovine lung surfactant by liquid chromatography. Deacylated SP-C (dSP-C), unchanged in composition and sequence from SP-C but having a decreased alpha-helical content in films with dipalmitoyl phosphatidylcholine (DPPC) of 52 versus 70%, was obtained by treatment with 0.1 M sodium carbonate buffer at pH 10. Surface activity was studied for SP-C and dSP-C combined with column-purified phospholipids (PPL) from calf lung surfactant or with synthetic phospholipids (DPPC or a synthetic phospholipid mixture (SPL) containing 50:35:15, DPPC:egg phosphatidylcholine:egg phosphatidylglycerol). Interfacial measurements included surface pressure time adsorption isotherms for dispersed surfactants with diffusion minimized, dynamic surface pressure area isotherms and respreading for films in the Wilhelmy balance, and overall surface tension lowering at physiologic cycling rate in oscillating bubble experiments. Dispersions of PPL:SP-C and SPL:SP-C rapidly adsorbed to high equilibrium surface pressures of 47-48 mN/m, significantly better than corresponding dispersions containing dSP-C. The adsorption of PPL:dSP-C was essentially unchanged from that of PPL alone, and the adsorption of SPL:dSP-C was improved only slightly over SPL alone. In Wilhelmy balance studies, dynamic respreading was significantly improved over phospholipids alone in films of SP-C plus PPL, SPL, or DPPC. Respreading was improved less markedly by dSP-C in corresponding films with SPL or DPPC and not at all in films with PPL. Maximum surface pressures were also higher in cycled films of SP-C versus dSP-C combined with PPL or SPL. In bubble experiments (37 degrees C, 20 cycles/min), dispersions of PPL:SP-C and SPL:SP-C reached low minimum surface tensions of <1 and 5 mN/m, respectively, whereas PPL:dSP-C and SPL:dSP-C only reached minima of approximately 20 mN/m as did PPL and SPL alone. Acylation in SP-C is crucial for its interactions with phospholipids over the full spectrum of adsorption and dynamic surface behaviors important for lung surfactant.

Evaluation of surfactant treatment strategies after prolonged graft storage in lung transplantation.

We have previously documented alterations in endogenous surfactant after lung transplantation and improved graft function in some dogs after instillation of bovine lipid extract surfactant (bLES) into the recipient. To determine the effect of bLES delivery method and timing of treatment on physiologic response and surfactant recovery, 21 canine left lung grafts were divided into four groups: (1) Treatment of the donor for 3 h with aerosolized bLES prior to graft storage (Donor Aerosol); (2) Treatment of the recipient with instilled bLES immediately after transplantation (Recipient Instilled); (3) No bLES treatment (Control); and (4) Aerosolized bLES in donors and instilled bLES in recipients (Combined Therapy). Aerosolized bLES was labeled with [3H]-dipalmitoylphosphatidylcholine (DPPC) and instilled bLES with [14C]-DPPC. Grafts were stored for 36 h, transplanted and reperfused for 6 h. The native right and transplanted left lungs were then lavaged and protein yield, surfactant aggregates, and bLES recovery were measured. After 6 h of reperfusion, PO2/FlO2 ratio was significantly better after Combined Therapy (372 +/- 52 mm Hg) than in the Recipient Instilled (117 +/- 47 mm Hg) and Control groups (87 +/- 26 mm Hg), with intermediate values in Donor Aerosol dogs (232 +/- 64 mm Hg). The recovery of donor aerosolized bLES from transplanted lungs was increased in dogs given Combined Therapy versus Donor Aerosol treatment alone (p = 0.03). Furthermore, with Combined Therapy there was an increased percentage of instilled bLES recovered from transplanted lungs compared with the Recipient Instilled group. We conclude that surfactant treatment strategies influence physiologic response and bLES recovery after prolonged lung preservation. Treatment of lung donors with exogenous surfactant prior to graft storage was associated with less severe lung injury. Combined donor and recipient bLES therapy resulted in a superior physiologic response during reperfusion in this model.

Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity.

1. It has been proposed to use exogenous pulmonary surfactant as a drug delivery system for antibiotics to the alveolar compartment of the lung. Little, however, is known about interactions between pulmonary surfactant and antimicrobial agents. This study investigated the activity of a bovine pulmonary surfactant after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or tobramycin. 2. Surfactant (1 mg ml-1 in vitro and 40 mg ml-1 in vivo) was mixed with 0.375 mg ml-1 amphotericin B, 50 mg ml-1 amoxicillin, 37.5 mg ml-1 ceftazidime, 1 mg ml-1 pentamidine and 2.5 mg ml-1 tobramycin. Minimal surface tension of 50 microliters of the mixtures was measured in vitro by use of the Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to restore gas exchange in an established rat model for surfactant deficiency. 3. Surfactant deficiency was induced in ventilated rats by repeated lavage of the lung with warm saline until PaO2 dropped below 80 cmH2O with 100% inspired oxygen at standard ventilation settings. Subsequently an antibiotic-surfactant mixture, saline, air, or surfactant alone was instilled intratracheally (4 ml kg-1 volume, n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min after instillation. 4. The results showed that minimal surface tensions of the mixtures were comparable to that of surfactant alone. In vivo PaO2 levels in the animals receiving ceftazidime-surfactant or pentamidine-surfactant were unchanged when compared to the surfactant group. PaO2 levels in animals receiving amphotericin B-surfactant, amoxicillin-surfactant or tobramycin-surfactant were significantly decreased compared to the surfactant group. For tobramycin it was further found that PaO2 levels were not affected when 0.2 M NaHCO3 (pH = 8.3) buffer was used for suspending surfactant instead of saline. 5. It is concluded that some antibiotics affect the in vivo activity of a bovine pulmonary surfactant. Therefore, before using surfactant-antibiotic mixtures in clinical trials, interactions between the two agents should be carefully evaluated.

IMPACT OF DIFFERENT SURFACTANT PREPARATIONS ON CD 62 L - EXPRESSION ON ACTIVATED NEUTROPHILS AND MONOCYTES † 2070

Introduction: The potential role of polymorphonuclear neutrophils(PMN) and macrophages in the pathogenesis of acute respiratory distress syndrome (ARDS) develops as a result of CD 62 L (L-selectin) mediated inflammatory-cell endothelial injury. Surfactant (SF) replacement therapy is gaining increased use in term infants and adults with ARDS. We therefore wanted to determine the effect of SF on CD 62-L expression of PMN and monocytes. Material and methods: Heparinized whole blood (5 ml) from healthy adult volunteers was incubated for 1 hour with 10-6 mol/ml N-formylmethionyl-leucylphenylalanin (fMLP) together with bovine SF(Alveofact®; Fa. Thomae, F.R.G.) and synthetic SF (Exosurf®, Wellcome, USA) (1,2 mg/ml). Elastase-α1 - proteinase inhibitor complex(E-PI) as a result of PMN-activation was determined by chemoluminescence immunoassay. Analyses of PMN and monocytes population as well as CD 62 L expression were performed on a FACScan flow cytometer (Becton Dickinson, F.R.G.). CD 62 L were expressed as percentage of positive stained cells.Results: After incubation with natural SF and fMLP decreased E-PI levels from 30% compared with E-PI levels after incubation with fMLP alone. Increased levels of E-PI of 90% after incubation with synthetic surfactant were found: Table Conclusion: In contrast to synthetic SF natural SF is able to inhibit PMN activation in vitro. After incubation with SF CD 62 L-expression is decreased, depending on the preparation used. From our data we conclude that SF treatment can influence inflammatory cell-mediated endothelial cell injury in the early stage of acute lung injury.

Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.

Use of surfactant in pulmonary disorders in full-term infants

Pulmonary surfactant is routinely used for treatment of premature babies with respiratory distress syndrome, and its use in full-term infants with respiratory failure is now under extensive clinical investigation. Several clinical reports have shown that intratracheal instillation of large doses of bovine and porcine lung-derived surfactant preparations has the potential to improve blood oxygenation and ventilation efficiency in full-term neonates with respiratory distress syndrome, meconium aspiration syndrome, pneumonia, pulmonary hemorrhage, and lung hypoplasia. These findings are suggestive of secondary surfactant deficiency or surfactant dysfunction in the pathogenesis of respiratory failure in full-term infants. Further clinical investigation with multicenter, randomized, controlled clinical trials is warranted to verify new indications of surfactant application for these diseases.

Timing of exogenous surfactant administration in a rabbit model of acute lung injury.

The purpose of this study was to evaluate early vs. late administration of exogenous surfactant in an adult rabbit model of acute lung injury. Lung injury was induced by repetitive whole lung saline lavage and subsequent mechanical ventilation. Bovine lipid extract surfactant was instilled either 1 (Early) or 4 h (Late) after the last lavage. Animals were monitored for 7 h after the last lavage. Although arterial PO2 values increased significantly immediately after treatment in both the Early and Late groups, this improvement was not sustained in the Late group. There was also a higher incidence of pneumothoraxes in the Late group vs. both the Early group and a nontreated control group. The ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates was higher in the Late group compared with the Early group. Morphological analysis revealed that early surfactant treatment prevented the progression of lung injury over time. We conclude that administration of exogenous surfactant at an early time point in lung injury resulted in superior responses compared with later treatments.