California 9581 7 (T.A.M.]In vitro data have shown a concentration-dependent inhibition of surfactant by meconium, while anecdotal reports demonstrate improved oxygenation after surfactant replacement in babies with meconium aspiration syndrome, particularly in conjunction with high-frequency jet ventilation. We randomized 70 newborn piglets to either conventional or high-frequency jet ventilation, followed by insufiation of 3 m W g of a 33% meconium solution. Each group was further randomized to one of five surfactant therapies: 1) control, 2) 4 m u g Survanta, 3) 8 m u g Survanta, 4) 5 m u g Exosurf, or 5) 10 m W g Exosurf. We followed arterial blood gases and ventilator requirements over 6 h of ventilation. Aspirates of airway fluids were obtained for surface tension measurements, as well as total protein and phospholipid concentrations. Using a previously established scoring system, a pathologist blinded to treatment evaluated four sections of lung per animal for histologic changes of meconium aspiration syndrome. There were no differences noted between groups in any physiologic parameter measured (mean airway pressure, arterial partial pressure of oxygenlalveolar partial pressure of oxygen ratio, etc.) during the 6 h of ventilation. Airway fluid aspirate total protein concentrations increased significantly after meconium instillation (4-to 5-fold,p < 0.007) and remained elevated in spite of surfactant therapy. There was an initial decline in airway phospholipid concentraThe MAS is a major cause of respiratory distress among neonates (20 000-30 000 babies are affected annu-

The serum components of C-reactive protein, lysophosphati-dylcholine, fibrinogen, and fibrinogen proteolytic products have been shown to reduce surface tension-lowering abilities of lung surfactant. The inhibitory effects of these serum components were compared among four different surfactants: natural lung surfactant, a phospholipid mixture that had no surfactant proteins, KL4 surfactant which has a synthetic surfactant protein B (SP-B)-like peptide, and beractant (BER) which has both SP-B and SP-C. The pulsating bubble surfactometer was used to measure the surface tension of these surfactants after the addition of inhibitors. Inhibition of BER and KL4 surfactant was observed with some serum components within 1 min of pulsation, but was reversed after 3 min of pulsation for KL4 surfactant and to a lesser extent with BER. The surface tension of phospholipid mixture alone was significantly increased and did not improve with further pulsations. Natural lung surfactant was least inhibited and was affected only at very high fibrinogen concentrations (5 mg/mL). At identical concentrations of these inhibitors, KL4 surfactant was inhibited less compared with BER. We conclude that the response of a lung surfactant to inhibitory agents may depend on the presence or absence of surfactant-related protein(s) in the surfactant and the concentration of exogenous surfactant used. KL4 surfactant, which has a synthetic peptide in lieu of SP-B, resists inhibition to these serum components more than BER at similar phospholipid concentrations.

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ABSTRACT. Previous studies in ret term lambs have Abbreviations --shown that exogenous surfactant is more uniformly distributed if given at birth before ventilation or if followed by high-frequency ventilation (HFV) after establishing conventional ventilation (CV). We hypothesized that the preterm rabbit pup would respond similarly and that improved respiratory system compliance (Crs) would accompany improved surfactant distribution. We randomized pups (27 d gestation) into three groups: control, surfactant at birth, and surfactant after 15 rnin of CV (rescue). We administered dipalmitoylphosphatidyl-[3H]choline-labe1ed natural surfactant by tracheostomy to each of the treated groups. The two treatment groups were treated for 15 rnin with either HFV or CV and subsequently with CV. We measured Crs at 15, 25,35, and 45 min after surfactant. Lungs from pups treated with CV or HFV (n = 89) for 15 min, with and without 30 rnin of subsequent (JV, were cut into 32 pieces that were counted for distribution of label or were sectioned for quantitative morphometry (n = 36).Pups receiving surfactant after 15 rnin of CV had higher Crs 15 rnin after surfactant than either pups treated with surfactant at birth or controls ( p < 0.001). The Crs of pups 15 rnin after rescue surfactant followed by HFV was lower than that of pups treated with CV ( p < 0.05) but was higher than that of either control or pups treated at birth groups ( p < 0.05). Crs at 35 and 45 rnin after surfactant were the same in all treatment groups. Application of HFV appeared to delay the delivery of surfactant to the distal airspaces. Differences in Crs paralleled differences in the uniformity of distribution of radiolabel. Distribution was more uniform in pups treated with CV than HFV after rescue ( p < 0.001) and after an additional 30 rnin of CV in both CV and HFV rescue groups. Aeration as judged by morphometry was similar in all treatment groups. These observations differ from previous reports and may be explained by differences in species, methods of HFV, or the use of natural surfactant containing surfactant-associated protein A versus lipid-extracted surfactant formulations containing solely lipophilic proteins. (Pediatr Res 31: 270-275,1992)