Sheep Surfactant Research Articles

Surface tension influences cell shape and phagocytosis in alveolar macrophages

The effect of surface tension on alveolar macrophage shape and phagocytosis was assessed in vivo and in vitro. Surface tension was regulated in vivo by conditionally expressing surfactant protein (SP)-B in Sftpb-/- mice. Increased surface tension and respiratory distress were produced by depletion of SP-B and were readily reversed by repletion of SP-B in vivo. Electron microscopy was used to demonstrate that alveolar macrophages were usually located beneath the surfactant film on the alveolar surfaces. Reduction of SP-B increased surface tension and resulted in flattening of alveolar macrophages on epithelial surfaces in vivo. Phagocytosis of intratracheally injected fluorescent microbeads by alveolar macrophages was decreased during SP-B deficiency and was restored by repletion of SP-B in vivo. Incubation of MH-S cells, a mouse macrophage cell line, with inactive surfactant caused cell flattening and decreased phagocytosis in vitro, findings that were reversed by the addition of sheep surfactant or phospholipid containing SP-B. SP-B controls surface tension by forming a surfactant phospholipid film that regulates shape and nonspecific phagocytic activity of alveolar macrophages on the alveolar surface.

Injury Responses to Different Surfactants in Ventilated Premature Lamb Lungs

The lung of the preterm infant is easily injured and an initial indication of the injury is an inflammatory response. Surfactant treatment and gentle ventilation will minimize the initiation and progression of injury. We asked if the initial lung injury response differed when preterm ventilated lambs were treated with complete natural sheep surfactant, a lipid extract of sheep surfactant, a surfactant used to treat RDS (Survanta®), or a synthetic surfactant containing recombinant SP-C (Venticute®). We used a gentle style of ventilation and a positive end expiratory pressure of 4 cmH20 to minimize injury. The surfactants were not distinguishable based on gas exchange, compliance or lung gas volumes over the 6h ventilation period. When compared with unventilated controls the ventilated lambs had increased protein and inflammatory cells in alveolar lavages. The cells from the alveolar lavages produced more H202, expressed more surface adhesion antigens and CD-14 receptors, and expressed more mRNA for the pro-inflammatory cytokines IL-1β and IL-8 than did cells from unventilated lungs. Lung tissue expressed primarily increased IL-6 mRNA relative to unventilated controls. However, there were no consistent differences in any of the inflammatory indicators between the different surfactant treated groups. Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung.

Injury responses to different surfactants in ventilated premature lamb lungs.

The lung of the preterm infant is easily injured and an initial indication of the injury is an inflammatory response. Surfactant treatment and gentle ventilation will minimize the initiation and progression of injury. We asked if the initial lung injury response differed when preterm ventilated lambs were treated with complete natural sheep surfactant, a lipid extract of sheep surfactant, a surfactant used to treat RDS (Survanta), or a synthetic surfactant containing recombinant SP-C (Venticute). We used a gentle style of ventilation and a positive end expiratory pressure of 4 cmH(2)0 to minimize injury. The surfactants were not distinguishable based on gas exchange, compliance or lung gas volumes over the 6h ventilation period. When compared with unventilated controls the ventilated lambs had increased protein and inflammatory cells in alveolar lavages. The cells from the alveolar lavages produced more H(2)0(2), expressed more surface adhesion antigens and CD-14 receptors, and expressed more mRNA for the pro-inflammatory cytokines IL-1 beta and IL-8 than did cells from unventilated lungs. Lung tissue expressed primarily increased IL-6 mRNA relative to unventilated controls. However, there were no consistent differences in any of the inflammatory indicators between the different surfactant treated groups. Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung.

Surfactant Protein C (SP-C) in Ventilated Premature Lamb Lung † 1677

Background. Synthetic surfactants have theoretical advantages of uniform composition, consistency of properties, lower risk, and lower cost. Synthetic surfactants that contain only lipids and recombinant SP-C can be as effective as natural surfactants for the treatment of surfactant deficiency in preterm animals. However, there is no information about the fate of this very hydrophobic protein in the preterm lung. Hypothesis. Because other surfactant components are cleared very slowly from the preterm lung, we hypothesized that SP-C would also be cleared slowly. Methods. We compared alveolar and total lung clearances of 125I-natural SP-C(nSP-C), 125I recombinant SP-C(rSP-C, phenylalanine in positions 4 and 5 and isoleucine in position 32 of the human sequence, provided by Byk Gulden, Konstanz, Germany) with the clearance of14 C-dipalmitoylphosphatidylcholine (DPC). Preterm lambs at 128 d gestation were given treatment doses of 100 mg/kg 125I-nSP-C labeled natural sheep surfactant (n=6), 125I-rSP-C labeled natural sheep surfactant (n=9) or 125I-rSP-C labeled synthetic surfactant (n=9) and recoveries were measured at 5 h. Trace doses of 125I-rSP-C and14 C-DPC also were given to 135 d gestation lambs without surfactant treatment and recoveries were measured at 0 (n=3), 2 (n=5), 5 (n=6), or 10 h(n=5). Results. 5 h after surfactant treatments, the 3 groups of lambs had the same pC02 values (50-54 mmHg), the same ventilator pressure requirements (18-20) cmH20, and similar compliances(0.46-0.51), indicating equivalent physiological lung function. The alveolar recoveries were 17-24% for 14C-DPC and 13-16% for labeled125 I-nSP-C and rSP-C for the 3 groups of lambs. Total lung recoveries were about 70% for the 14C-DPC and labeled nSP-C and rSP-C. All recoveries for nSP-C and rSP-C were similar and similar to those for DPC. In 135 d GA lambs not treated with surfactant,% recovery of 14C-DPC in alveolar lavage decreased from 45.2±2.5(0 h) to 11.3±0.4 at 10 h. There was no loss of the 14C-DPC from the total lungs. The recoveries of 125I-rSP-C decreased from 42.0±2.4% (0 h) in the alveolar lavage to 6.4±1.0% (10 h). Although about 20% of the radiolabeled rSP-C was lost from the total lung over first 2 h, there were no further loss to 10 h. Conclusions. The surfactants containing rSP-C and nSP-C were functionally similar and the two SP-C proteins were cleared slowly and in parallel with DPC.

Lung function in premature lambs and rabbits treated with a recombinant SP-C surfactant.

We evaluated the efficacy of a recombinant surfactant protein-C (rSP-C) surfactant in vitro and in vivo, using ventilated preterm lambs and rabbits. The surface tension measured with a Wilhelmy balance of the rSP-C surfactant was lower than the surface tension of natural sheep surfactant (containing SP-B and SP-C). The rSP-C and natural surfactants were equivalently sensitive to inhibition by plasma. Over a 5-h study period, lambs treated with 100 mg/kg rSP-C and natural surfactants at birth had similar PCO2, lung mechanics, and FRC values. Indicators of injury also were not different. In preterm rabbits ventilated with 3 cm H2O positive end-expiratory pressure (PEEP), similar compliance responses were measured for the rSP-C and natural surfactant. Large-aggregate surfactants recovered from alveolar washes of the lambs treated with rSP-C or natural surfactant retained their function when tested in preterm rabbits. In conclusion, the rSP-C surfactant was effective in preterm animals with surfactant deficiency.

Effects of ventilation style on surfactant metabolism and treatment response in preterm lambs.

We investigated whether the style of ventilation would influence respiratory physiology or surfactant metabolism in surfactant-treated preterm lambs. Preterm lambs were delivered at 131 +/- 1 d gestation and treated with an organic solvent extract of sheep surfactant (100 mg/kg). The lambs were randomized to ventilation peiods of 2 h, 5 h, 10 h, or 24 h, and to ventilation with a low rate (15 breaths/min) and high VT (15 ml/kg), with a high rate (50 breaths/min) and low VT (8 ml/kg), or with high-frequency oscillatory ventilation (HFOV). Gas exchange and lung volumes were similar across time and for the different ventilation styles. Saturated phosphatidylcholine (SatPC) in alveolar lavage was lower for the HFOV group than for the other ventilation groups at 10 h and 24 h. The rate of loss of surfactant protein B (SP-B) from these preterm animals' lungs was slow and not influenced by ventilation style. The percentages of surfactants in large-aggregate forms were not changed by style of ventilation, and the large-aggregate surfactants had excellent function when tested in surfactant-deficient preterm rabbits. Alveolar lavage protein was low (30 ml/kg), and tissue hyaluronan did not change with time or ventilation style. In preterm lambs ventilated without causing injury, the extreme styles of ventilation examined in the study had minimal effects on lung function, surfactant function, or surfactant metabolism.

Effects of Ventilation Style on Surfactant Treatment Response in Premature Lambs. † 910

Effects of ventilation style on long term responses to surfactant have not been studied in the surfactant treated preterm. Preterm lambs were delivered at 130±1 d gestation (term 150 d) and treated with 100 mg/kg lipid extracted sheep surfactant. Three styles of ventilation that are at the extremes of clinical practice were used: (L) low rate of 15 breath/min, tidal volume 13 ml/kg; (H) high rate of 50 breath/min, tidal volume 8 ml/kg; (HFV) Sensomedics 3100 high frequency ventilation. Normal blood gas values(PCO2 45-50 mmHg) were achieved for all animals. Groups of 4 to 6 lambs(total N=60) were killed at 2, 5, 10 and 24h to recover alveolar wash (AW) and lung tissue for biochemical analysis. Mean airway pressure (MAP, cmH2O), dynamic compliance (Comp. ml/cmH2O·kg), functional residual capacity (FRC, ml/kg), lung volume at 40 cmH2O(V40, ml/kg),% functional large aggregate surfactant (%L) in AW, total protein in AW (protein, mg/kg) at 24h of age are in the table.

Effect of Coating with Lung Lining Fluid on the Ability of Fibres to Produce a Respiratory Burst in Rat Alveolar Macrophages

The aim of the study was to develop a simple short-term in vitro assay which would allow us to predict the pathogenicity of fibres based on data already available from in vivo studies. Fibres were used naked (uncoated) or coated with rat IgG, or rat or sheep surfactant. The fibres were used to stimulate superoxide anion release by rat alveolar macrophages. Binding of fibres to rat alveolar macrophages was assessed by optical microscopy. Fibres used in the naked state produced little or no stimulation of superoxide anion from rat alveolar macrophages. When fibres were coated with rat IgG there was a significant increase in superoxide release for all fibre types with the exception of RCF4 and Code 100/475. When fibres were coated with rat or sheep surfactant, there was suppression of the respiratory burst for all fibre types. The observed suppression was not due to a scavenging effect by the surfactant itself, because xanthine/xanthine oxidase generated superoxide was unaffected by surfactant. The suppressive effect was shown to act directly on the macrophages. Comparing naked and coated fibres for their ability to bind to macrophages, it was shown that in general more coated fibres were bound and that increased binding was associated with suppressed superoxide release for both types of surfactant-coated fibres. It was concluded that the nature of the fibre coating is the main factor influencing the interaction between fibres and macrophages. The type of binding through different receptors may either stimulate or switch off the respiratory burst. The assay used here does not, however, allow any predictions to be made regarding the pathogenicity of fibres.

Surfactant inhibition by plasma: gestational age and surfactant treatment effects in preterm lambs.

The preterm infant with respiratory distress syndrome has edematous lungs and small amounts of surfactant that do not function normally. We reported that surfactant recovered from preterm lambs after surfactant treatment can have decreased sensitivity to inhibition of surface tension by plasma. We asked whether this augmented resistance to inhibition was dependent on lung development (gestational age) by testing sensitivity to plasma inhibition of 1) endogenous surfactant from preterm lambs and 2) surfactant from preterm lambs after treatment with an organic solvent-extracted natural sheep surfactant. Surfactant recovered after surfactant treatment of 121- or 128-days-gestation lambs had the same sensitivity to plasma inhibition as did the surfactant used to treat the lambs. Surfactant recovered from 134-days-gestation lambs had decreased sensitivity to inhibition. Lung maturation is a variable influencing surfactant inhibition by plasma.

Surfactant treatment and ventilation effects on surfactant SP-A, SP-B, and SP-C mRNA levels in preterm lamb lungs

The effects of exogenous surfactant treatment combined with postnatal ventilation on surfactant protein (SP)-A, SP-B, and SP-C steady-state mRNA levels were evaluated in preterm sheep at 120, 132, and 139 days gestation. Three groups were studied at each gestation period: animals ventilated and treated with 100 mg/kg natural sheep surfactant, animals ventilated and not treated with surfactant, and a comparison group of lambs that were neither ventilated nor treated with surfactant. In unventilated lambs, SP-A and SP-C mRNA levels measured by densitometry from Northern blots increased between 120 and 132 days gestation (P < 0.05). At 120 days gestation, no differences in SP-A, SP-B, or SP-C mRNA levels were noted among the three groups. At 132 days gestation, SP-A mRNA levels increased in both ventilated groups (P < 0.01), but no additional surfactant effect on SP-A mRNA expression was detected. There were no changes in SP-B or SP-C mRNA levels among the groups at 132 days gestation. At 139 days gestation, mRNA levels for both SP-A and SP-B increased after ventilation, compared with the unventilated groups (P < 0.05). Furthermore, an additional effect of surfactant treatment to increase SP-A mRNA levels relative to animals undergoing ventilation alone was noted (P < 0.05). We conclude that postnatal changes in mRNA levels for the surfactant proteins are gestationally regulated and protein specific.

Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant.

The effect of the addition of surfactant protein (SP)-B or SP-B plus SP-C (SP-BC) to a surfactant made from bovine lung (Survanta) was evaluated in 27-d-gestation preterm rabbits. The animals were treated with Survanta, Survanta + 2% SP-B, Survanta + 3% SP-BC, or sheep surfactant. They were then ventilated with 3 cm H2O positive end-expiratory pressure and tidal volumes of 8 mL/kg. Survanta + 2% SP-B was prepared by adding SP-B in water to Survanta or by adding SP-B in chloroform [SP-B(Chl)] to lipid-extracted Survanta. Dynamic compliances of the Survanta + 2% SP-B(Chl)- and Survanta + 3% SP-BC-treated rabbits were greater (p < 0.05) than those treated with Survanta or Survanta + 2% SP-B in water and were comparable to sheep surfactant. Postventilation pressure-volume curves for the groups treated with Survanta supplemented with SP-B had significantly larger retained volumes on deflation compared with those treated only with Survanta (p < 0.01). The effects of ventilation style on the responses were assessed by ventilating other groups of rabbits treated with Survanta, Survanta + 0.5% SP-B(Chl), Survanta + 2% SP-B(Chl), or sheep surfactant with tidal volumes of 10 mL/kg and 0 cm H2O positive end-expiratory pressure. SP-B (2%) augmented the in vivo function of Survanta without positive end-expiratory pressure, and 0.5% SP-B had no effect. Infasurf, a surfactant with more SP-B, was more effective than Survanta when tested in the preterm rabbits. SP-B is a critical factor for optimum immediate surfactant function.

Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment

We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant-deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age.

Lung parenchyma and type II cell morphometrics: effect of surfactant treatment on preterm ventilated lamb lungs

The effect of exogenous surfactant treatment on lung and type II cell structure of ventilated lambs of 137-138 days gestational age was studied. Thirty-four lambs were delivered and randomized to control or 100 mg/kg of natural sheep surfactant treatment groups. Lungs from one group of lambs not treated with surfactant were fixed before ventilation, and the other animals were ventilated to maintain normal blood gas values for 3, 24, or 48 h. Morphometric assessment of the inflation-fixed lung parenchyma of ventilated lungs was compared with the architectural appearance of alveoli and alveolar ducts in the unventilated lungs. Mechanical ventilation resulted in distension of alveolar ducts accompanied by the shallowing and loss of well-defined alveoli and areas of atelectasis at 3 h. These abnormalities increased in severity after 24 and 48 h of ventilation. Surfactant treatment before ventilation significantly reduced the extent and degree of dilatation and concomitant atelectasis. The fraction of normal parenchyma was 38 +/- 7% in untreated lambs vs. 64 +/- 6% in treated lambs after 24 h of ventilation. After 48 h of ventilation, significant differences between control (39 +/- 6%) and surfactant-treated (55 +/- 6%) lambs were still evident. Alveolar type II cells contained approximately 15% lamellar bodies by volume. Neither surfactant treatment nor time of ventilation altered the volume density of lamellar bodies or other organelles, except for a decrease in glycogen from 8% in nonventilated lungs to 2.5% in lungs ventilated for 24 h. These findings indicate that a surfactant treatment at birth results in the maintenance of more normal parenchyma with less atelectasis during prolonged ventilation of the immature lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Different ventilation strategies alter surfactant responses in preterm rabbits.

The effect of ventilation strategy on in vivo function of different surfactants was evaluated in preterm rabbits delivered at 27 days gestational age and ventilated with either 0 cmH2O positive end-expiratory pressure (PEEP) at tidal volumes of 10-11 ml/kg or 3 cmH2O PEEP at tidal volumes of 7-8 ml/kg after treatment with one of four different surfactants: sheep surfactant, the lipids of sheep surfactant stripped of protein (LH-20 lipid), Exosurf, and Survanta. The use of 3 cmH2O PEEP decreased pneumothoraces in all groups except for the sheep surfactant group where pneumothoraces increased (P < 0.01). Ventilatory pressures (peak pressures - PEEP) decreased more with the 3 cmH2O PEEP, low-tidal-volume ventilation strategy for Exosurf-, Survanta-, and sheep surfactant-treated rabbits (P < 0.05), whereas ventilation efficiency indexes (VEI) improved only for Survanta- and sheep surfactant-treated rabbits with 3 cmH2O PEEP (P < 0.01). Pressure-volume curves for sheep surfactant-treated rabbits were better than for all other treated groups (P < 0.01), although Exosurf and Survanta increased lung volumes above those in control rabbits (P < 0.05). The recovery of intravascular radiolabeled albumin in the lungs and alveolar washes was used as an indicator of pulmonary edema. Only Survanta and sheep surfactant decreased protein leaks in the absence of PEEP, whereas all treatments decreased labeled albumin recoveries when 3 cmH2O PEEP was used (P < 0.05). These experiments demonstrate that ventilation style will alter a number of measurements of surfactant function, and the effects differ for different surfactants.

Lung albumin recovery in surfactant-treated preterm ventilated lambs.

Preterm ventilated animals and infants with respiratory distress syndrome (RDS) develop proteinaceous alveolar edema. To study the effect of postnatal age on intravascular radiolabeled albumin accumulation into lungs, preterm lambs at 132 days gestational age were ventilated after treatment with sheep surfactant or cow surfactant extract for periods as long as 24 h. Lambs not treated with surfactant were studied for only 5 h because of severe respiratory failure. All lambs were given radiolabeled albumin by intravascular injection 1 h before they were killed, and the net recovery of the labeled albumin was measured in the lung tissue and air space as quantified by alveolar lavage. Net 1-h radiolabeled albumin recoveries in the lungs decreased from 5 to 6% soon after birth to 0.9% at 24 h in the surfactant-treated groups (p less than 0.01). At 3 h there was less labeled albumin recovery by alveolar lavages in lambs treated with sheep surfactant than in control lambs and lambs treated with cow surfactant extract (p less than 0.05). Protein in alveolar washes from lambs treated with cow surfactant extract exceeded that in lambs treated with sheep surfactant at 3 h (p less than 0.05), but protein recoveries had decreased to similar values by 24 h, indicating a net clearance of air-space protein. These studies demonstrate a sixfold decrease in net albumin accumulation from birth to 24 h of age despite continued ventilation and oxygen exposure of the premature lamb lungs.

Corticosteroids, Thyrotropin-Releasing Hormone, and Antioxidant Enzymes in Preterm Lamb Lungs

Forty-three twin lamb fetuses of 121 +/- 1 d gestation were catheterized and received i.v. saline (n = 8), 0.75 mg/kg/h cortisol for 60 h (n = 15), 5 micrograms/kg thyrotropin-releasing hormone (TRH) every 12 h for five doses (n = 9), or cortisol and TRH (n = 11) before delivery at 128 +/- 1 d. After delivery, the lambs were randomized for natural sheep surfactant treatment or sham treatment, ventilated for 75 min, and killed. Superoxide dismutase, catalase, and glutathione peroxidase activities were measured in fetal lung tissue. Superoxide dismutase and catalase activities were increased in both the corticosteroid (p less than 0.001) and the corticosteroid with TRH (p less than 0.01) groups. Glutathione peroxidase activity was higher after prenatal corticosteroid treatment, but statistical significance was not reached (p = 0.06). Although prenatal exposure to corticosteroids increased superoxide dismutase, catalase, and glutathione peroxidase activities, TRH alone or TRH added to corticosteroids provided no additional benefit. Lambs treated with surfactant had higher lung catalase activities than lambs that did not receive surfactant, probably secondary to the presence of catalase activity in the surfactant preparation. Increased pulmonary antioxidant enzyme activity may be an additional feature of the overall beneficial effect of corticosteroids on fetal lung development.

Surfactant metabolism in surfactant-treated preterm ventilated lambs.

Preterm lambs were delivered at 132 days gestational age, treated with 100 mg/kg radiolabeled natural sheep surfactant or Surfactant TA, and ventilated for times up to 24 h. Compared with an untreated group that developed respiratory failure by 5 h, both surfactant-treated groups had stable respiratory function to 24 h. Although only approximately 13% of the labeled surfactant phosphatidylcholine was recovered by alveolar wash at 24 h, there was no significant loss of the labeled phosphatidylcholine from the lungs. Labeled palmitic acid intravascularly injected at 1 h of age comparably labeled lung phosphatidylcholine in the three groups of lambs at 5 h; however, only approximately 0.5% of the labeled phosphatidylcholine was secreted to the air spaces of surfactant-treated lambs at 24 h. Labeled lysophosphatidylcholine given with the natural sheep surfactant was taken up by the lungs, converted to phosphatidylcholine with 30-40% efficiency, and resecreted to the air spaces, demonstrating recycling of a phospholipid. The large surfactant aggregates recovered from alveolar washes by centrifugation were surface active and contained approximately 76% of the air-space phosphatidylcholine in both surfactant-treated groups. Although clinical status was comparable, alveolar washes and surfactant subfractions from Surfactant TA-treated lambs had better surface properties than did sheep surfactant-treated lambs. These studies identified no detrimental effects of surfactant treatments on endogenous surfactant metabolism and indicated that the surfactants used for treatments were recycled by the preterm ventilated lamb lung.

Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs.

Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs.

1 COMPARISON OP TWO SURFACTANTS: IN VITRO SURFACE PROPERTIES AND EARLY EFFECTS IN SURFACTANT DEFICIENT RABBITS

In search of the most effective surfactant to use for surfactant replacement therapy, we compared an artificial porcine derived (APS) and neutral sheep surfactant preparation (NSS) with respect to in vitro characteristics and in vivo early effects. In 6 animals APS and 6 others NSS was administered endotracheally. Results: APS had the lowest in vitro minimal surface tension, 7 vs. 21 mN/m (Wilhelmy balance) and nearly zero vs. 22 mN/m (oscillating bublle) and a larger hysteresis compared to NSS. Within 1 min. following endotracheal surfactant instillation, however, PaO2 increased to significantly higher levels in the NSS group animals: 48.9 ± 16.2 vs. 25.1 ± 12.0 kPa (mean±SD, p<0.05). Similarly, static lung compliance was significantly higher in the NSS group: 1.04 ± 0.33 vs. 0.06±0.10 ml/cmH2O/kg body weight (p<0.05). We conclude that early in vivo effects of surfactant preparations do not seem to relate to in vitro properties.

Discussion

Discussion