Ikegami M, Jobe A, Jacobs H, Jones S J
J Clin Invest. 1981 Aug;68(2):491-6. doi: 10.1172/jci110280.
To test an artificial surfactant in vivo, six 120-d gestational age lambs were treated at birth with a mixture of a 9:1 M ratio of [14C]dipalmitoyl phosphatidylcholine (DPC) and phosphatidylglycerol at a dose of 100 mg DPC/kg. Nine other lambs were not treated. The mean PO2 values of the lambs treated with artificial surfactant were 65.7 +/- 11 mm Hg vs. 24.8 +/- 1.6 mm Hg for the untreated lambs (P less than 0.001). All lambs then were treated with 50 mg/natural surfactant lipid per kg, which promptly improved PO2 in all lambs. The PO2 values of those lambs previously treated with artificial surfactant remained greater than 100 mm Hg for 2.5 +/- 0.5 h vs. 0.9 +/- 0.3 h for lambs untreated with artificial surfactant (P less than 0.01). The pH and PCO2 values were not strikingly different between the two groups of lambs. Airway samples taken from lambs treated with artificial surfactant before treatment with natural surfactant had minimal surface tensions of 32 +/- 2.9 dyn/cm, whereas the artificial surfactant reisolated from these samples by centrifugation had minimum surface tension of 0 dyn/cm. The minimum surface tension of artificial surfactant was inhibited by fetal lung fluid from the premature lambs, whereas the minimum surface tension of natural surfactant was much less sensitive to inhibition. Artificial surfactant did not improve the pressure-volume characteristics of unventilated premature lung, whereas natural surfactant did. The change in specific activity of [14C]DPC following treatment with natural surfactant indicated that approximately 50% of the DPC initially administered was no longer associated with the airways.
为了在体内测试一种人工表面活性剂,对6只妊娠120天的羔羊在出生时用[¹⁴C]二棕榈酰磷脂酰胆碱(DPC)与磷脂酰甘油以9:1摩尔比混合的制剂进行治疗,剂量为100mg DPC/kg。另外9只羔羊未接受治疗。接受人工表面活性剂治疗的羔羊的平均动脉血氧分压(PO₂)值为65.7±11mmHg,而未治疗的羔羊为24.8±1.6mmHg(P<0.001)。然后所有羔羊均接受每千克50mg天然表面活性剂脂质的治疗,这迅速改善了所有羔羊的PO₂。先前接受人工表面活性剂治疗的羔羊的PO₂值在2.5±0.5小时内保持大于100mmHg,而未接受人工表面活性剂治疗的羔羊为0.9±0.3小时(P<0.01)。两组羔羊的pH值和二氧化碳分压(PCO₂)值没有显著差异。在用天然表面活性剂治疗之前,从接受人工表面活性剂治疗的羔羊获取的气道样本的最小表面张力为32±2.9达因/厘米,而通过离心从这些样本中重新分离出的人工表面活性剂的最小表面张力为0达因/厘米。人工表面活性剂的最小表面张力受到早产羔羊肺液的抑制,而天然表面活性剂的最小表面张力对抑制的敏感性要低得多。人工表面活性剂并未改善未通气的早产肺的压力-容积特性,而天然表面活性剂则可以。在用天然表面活性剂治疗后,[¹⁴C]DPC比活性的变化表明,最初给予的DPC中约50%不再与气道相关。