Gortner Ludwig, Maroske Wiebke, Reiss Irwin, Weller Eberhard
Department of Pediatrics and Neonatology, University of the Saarland, Homburg/Saar Germany.
Arzneimittelforschung. 2006;56(1):25-32. doi: 10.1055/s-0031-1296697.
Surfactant therapy does not lead to a uniform, optimal and sustained effect on gas exchange in neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). The aim of the present study therefore was to compare the effects of a lipid-enriched and protein-modified natural surfactant preparations with a licensed, clinically used bovine surfactant preparation - SF-Ril (Alveofact).
SF-Ril was enriched with phosphatidylglycerol, sphingomyeline, phosphatidylethanolamine plasmalogen, phosphatidylethanolamine. Furthermore, SF-Ril was modified with increased surfactant protein B (SP-B)/surfactant protein C (SP-C) content and finally a mercaptoethanol (ME) treated preparation for breaking the sulfhydril bondage of SP-B/SP-C by chemical reduction in methylene chloride using ME was developed. Finally ME was removed by vacuum extraction. These modified surfactants were tested at a dosage of 100 mg/ kg each in a model of respiratory failure induced by lung lavage in male adult rats and compared with SF-Ril at an identical dosage. Mechanical ventilation was standardised with fraction of inspiratory oxygen (FiO2) 1.0 and time-cycled pressure limited ventilation 16/0.8 cmH2O before and 26/6 cmH2O (peak inspiratory pressure/positive endexpiratory pressure) after lung lavage (target arterial oxygen pressure [pa02] < 100 mmHg), respiratory rate 36/min, inspiration/expiration time ratio 1:2.
During the observation period of 120 min, the sphingomyeline substituted and protein-modified (ME reduced) surfactant preparations exerted improved and sustained oxygenation compared with SF-Ril. Similar effects were observed for tidal volumes. All other preparations were equal or inferior to SF-Ril in our model.
For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models.
表面活性剂疗法对新生儿呼吸窘迫综合征（RDS）和急性呼吸窘迫综合征（ARDS）的气体交换并未产生一致、最佳且持久的效果。因此，本研究的目的是比较一种富含脂质且蛋白质修饰的天然表面活性剂制剂与一种已获许可、临床使用的牛表面活性剂制剂——SF-Ril（肺泡表面活性物质）的效果。
SF-Ril富含磷脂酰甘油、鞘磷脂、缩醛磷脂酰乙醇胺、磷脂酰乙醇胺。此外，通过增加表面活性剂蛋白B（SP-B）/表面活性剂蛋白C（SP-C）的含量对SF-Ril进行修饰，最后开发出一种经巯基乙醇（ME）处理的制剂，该制剂通过在二氯甲烷中使用ME进行化学还原以打破SP-B/SP-C的巯基键。最后通过真空萃取去除ME。在成年雄性大鼠肺灌洗诱导的呼吸衰竭模型中，以每千克100毫克的剂量对这些修饰后的表面活性剂进行测试，并与相同剂量的SF-Ril进行比较。在肺灌洗前，机械通气以吸入氧分数（FiO2）1.0和时间切换压力限制通气16/0.8厘米水柱进行标准化，肺灌洗后以26/6厘米水柱（吸气峰压/呼气末正压）进行标准化（目标动脉血氧分压[paO2]<100毫米汞柱），呼吸频率36次/分钟，吸呼时间比1:2。
在120分钟的观察期内，与SF-Ril相比，鞘磷脂替代且蛋白质修饰（ME还原）的表面活性剂制剂表现出改善且持久的氧合作用。潮气量也观察到类似效果。在我们的模型中，所有其他制剂与SF-Ril相当或更差。
对于开发不易失活的表面活性剂制剂，上述数据可能提供有用信息，前提是它们能在采用其他替代模型的进一步研究中得到证实。
