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)
Infants with chronic lung disease have acute episodes of hypoxemia that are often accompanied by wheezing. To test whether a sudden reduction in FIO2 might increase airway obstruction in such infants, we measured the flow-volume relationship, O2 saturation, and skin-surface CO2 tension in 19 sedated infants, 11 with chronic lung disease, and 8 control infants, before and during 10 min of continuous hypoxemia. In the infants with chronic lung disease, a 20 to 25% reduction in FIO2 caused acute hypoxemia (O2 saturation, 77 +/- 8%) and an associated decrease in mid-expiratory flow from 103 +/- 55 to 69 +/- 37 ml/s (mean +/- SD; p less than 0.05) in the absence of a significant change in tidal volume or skin-surface CO2 tension. In the infants without lung disease, breathing 17% O2 led to a significant increase in minute ventilation (26 +/- 25%; p = 0.05), but there was no consistent change in mid-expiratory flow. To further study the effects of an acute reduction in FIO2 on pulmonary function in infants with chronic lung disease, we measured lung mechanics in 6 infants and end-expiratory lung volume in 5. Baseline lung resistance was high (49 +/- 35 cm/l/s) and increased by 55 +/- 30% (p less than 0.05) in response to hypoxemia. Baseline dynamic lung compliance was low (2.5 +/- 1.5 ml/cm) and decreased by 24 +/- 10% (p less than 0.05). Functional residual capacity increased from 26 +/- 13 to 33 +/- 14 ml/kg (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Exogenous surfactant therapy has been recognised as an approach to alleviating the surfactant-deficine state for 3 decades. Natural and lipid-extracted surfactants derived from amniotic fluid, lung lavage, or lung homogenates are being used in worldwide clinical trials in premature infants. These studies are demonstrating a generally favourable influence on lung function by improving oxygenation and reducing the risk for pneumothorax and pulmonary interstitial emphysema. In some studies, reduction in death and the occurrence of bronchopulmonary dysplasia have been found. Numerous questions are unresolved and pharmacokinetic data are limited in preterm infants. Artificial surfactants are similarly under evaluation but current data demonstrate less overall effect. Adult respiratory distress syndrome has also been treated with exogenous surfactants. Although complex in terms of multiple initiating factors and in terms of high permeability of surfactant inhibitors, further studies are under way to determine the ideal methods of administration to enhance distribution and to monitor surfactant function in vivo.
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