Häfner D, Germann P G, Hauschke D, Kilian U
Department of Respiratory Pharmacology, Byk Gulden, Konstanz, Germany.
Pulm Pharmacol Ther. 1999;12(3):193-201. doi: 10.1006/pupt.1999.0201.
Surfactant treatment in patients with acute respiratory distress syndrome (ARDS) may be a promising treatment strategy. The aim of this study was to investigate whether addition of a recombinant surfactant protein C (rSP-C) to a plain phospholipid (PL) surfactant (PL surfactant) can result in activity comparable to commercially available surfactant preparations (Alveofact and bLES) which contain surfactant protein B and C. In this investigation dose-response comparisons of four surfactants were performed in an animal model of ARDS induced by total lung lavage. The surfactants were given shortly (;10 min) after the last lavage. The effects of surfactant treatment were compared with respect to improve oxygenation and to prevent histopathological changes, such as hyaline membrane formation. The surfactants were compared to lavaged, untreated controls. The surfactants were administered at doses of 25, 50 and 100 mg total amount of phospholipids/kg body weight. At 120 min after early treatment, all three doses of rSP-C surfactant showed statistically significant higher improvements in oxygenation than PL surfactant. This improvement was comparable to bLES and superior to Alveofact. The rSP-C surfactant showed the most prominent effect on preventing hyaline membrane formation. It was again superior to PL surfactant and comparable to bLES. It is concluded that addition of rSP-C enhances the activity of a pure PL surfactant. The rSP-C surfactant showed comparable or even superior activity to bovine-derived surfactant preparations containing both, SP-B and SP-C.
在急性呼吸窘迫综合征(ARDS)患者中进行表面活性剂治疗可能是一种有前景的治疗策略。本研究的目的是调查在普通磷脂(PL)表面活性剂(PL表面活性剂)中添加重组表面活性蛋白C(rSP-C)是否能产生与含有表面活性蛋白B和C的市售表面活性剂制剂(Alveofact和bLES)相当的活性。在本研究中,在全肺灌洗诱导的ARDS动物模型中对四种表面活性剂进行了剂量反应比较。在最后一次灌洗后不久(约10分钟)给予表面活性剂。比较表面活性剂治疗在改善氧合和预防组织病理学变化(如透明膜形成)方面的效果。将表面活性剂与灌洗的未治疗对照进行比较。表面活性剂以25、50和100mg磷脂总量/千克体重的剂量给药。在早期治疗后120分钟,所有三种剂量的rSP-C表面活性剂在氧合改善方面均显示出统计学上显著高于PL表面活性剂。这种改善与bLES相当,且优于Alveofact。rSP-C表面活性剂在预防透明膜形成方面显示出最显著的效果。它再次优于PL表面活性剂,且与bLES相当。得出的结论是,添加rSP-C可增强纯PL表面活性剂的活性。rSP-C表面活性剂显示出与含有SP-B和SP-C的牛源性表面活性剂制剂相当甚至更优的活性。