van Zyl Johann M, Smith Johan, Hawtrey Arthur
Division of Pharmacology, Cape Town, South Africa.
Drug Des Devel Ther. 2013;7:139-48. doi: 10.2147/DDDT.S40622. Epub 2013 Mar 11.
Currently, a new generation of synthetic pulmonary surfactants is being developed that may eventually replace animal-derived surfactants used in the treatment of respiratory distress syndrome. Enlightened by this, we prepared a synthetic peptide-containing surfactant (Synsurf) consisting of phospholipids and poly-l-lysine electrostatically bonded to poly-l-glutamic acid. Our objective in this study was to investigate if bronchoalveolar lavage (BAL)-induced acute lung injury and surfactant deficiency with accompanying hypoxemia and increased alveolar and physiological dead space is restored to its prelavage condition by surfactant replacement with Synsurf, a generic prepared Exosurf, and a generic Exosurf containing Ca(2+).
Twelve adult New Zealand white rabbits receiving conventional mechanical ventilation underwent repeated BAL to create acute lung injury and surfactant-deficient lung disease. Synthetic surfactants were then administered and their effects assessed at specified time points over 5 hours. The variables assessed before and after lavage and surfactant treatment included alveolar and physiological dead space, dead space/tidal volume ratio, arterial end-tidal carbon dioxide tension (PCO2) difference (mainstream capnography), arterial blood gas analysis, calculated shunt, and oxygen ratios.
BAL led to acute lung injury characterized by an increasing arterial PCO2 and a simultaneous increase of alveolar and physiological dead space/tidal volume ratio with no intergroup differences. Arterial end-tidal PCO2 and dead space/tidal volume ratio correlated in the Synsurf, generic Exosurf and generic Exosurf containing Ca(2+) groups. A significant and sustained improvement in systemic oxygenation occurred from time point 180 minutes onward in animals treated with Synsurf compared to the other two groups (P < 0.001). A statistically significant decrease in pulmonary shunt (P < 0.001) was found for the Synsurf-treated group of animals, as well as radiographic improvement in three out of four animals in that group.
In general, surfactant-replacement therapy in the animals did not fully restore the lung to its prelavage condition. However, our data show that the formulated surfactant Synsurf improves oxygenation by lowering pulmonary shunt.
目前，新一代合成肺表面活性剂正在研发中，最终可能会取代用于治疗呼吸窘迫综合征的动物源性表面活性剂。受此启发，我们制备了一种含合成肽的表面活性剂（Synsurf），它由磷脂和与聚-L-谷氨酸静电结合的聚-L-赖氨酸组成。我们在本研究中的目的是调查通过用Synsurf、一种通用的Exosurf制剂以及一种含Ca(2+)的通用Exosurf替代表面活性剂，支气管肺泡灌洗（BAL）诱导的急性肺损伤以及伴有低氧血症和肺泡及生理死腔增加的表面活性剂缺乏是否能恢复到灌洗前状态。
12只接受常规机械通气的成年新西兰白兔接受反复BAL以造成急性肺损伤和表面活性剂缺乏性肺病。然后给予合成表面活性剂，并在5小时内的特定时间点评估其效果。在灌洗和表面活性剂治疗前后评估的变量包括肺泡和生理死腔、死腔/潮气量比、动脉呼气末二氧化碳分压（PCO2）差值（主流二氧化碳图）、动脉血气分析、计算分流和氧比。
BAL导致急性肺损伤，其特征为动脉PCO2升高，同时肺泡和生理死腔/潮气量比增加，组间无差异。Synsurf组、通用Exosurf组和含Ca(2+)的通用Exosurf组中，动脉呼气末PCO2与死腔/潮气量比相关。与其他两组相比，用Synsurf治疗的动物从180分钟时间点起全身氧合有显著且持续的改善（P < 0.001）。在接受Synsurf治疗的动物组中发现肺分流有统计学显著降低（P < 0.001），且该组四只动物中有三只在影像学上有改善。
总体而言，动物中的表面活性剂替代疗法未使肺完全恢复到灌洗前状态。然而，我们的数据表明，配制的表面活性剂Synsurf通过降低肺分流改善了氧合。
