Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study

Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration syndrome (MAS), is produced by bronchiolar obstruction and surfactant inactivation. It has been shown that substances in meconium, e.g. fatty acids, inhibit surfactant activity. However, the role of the enzyme phospholipase A2 (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome (ARDS), has not yet been studied. Our objective was to investigate whether PLA2 is present in meconium and inhibits pulmonary surfactant activity in vitro. Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns, was measured by the formation of lysophosphatidylcholine after incubation of meconium with radioactively labelled dipalmitoylphosphatidylcholine. Meconium was fractionated by Sephadex G-100 column chromatography and the fractions were assayed for PLA2 activity. Also, their effect on the surface tension of surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS). PLA2 activity was present in all meconium samples. Addition of meconium to surfactant significantly increased surface tension (mean +/- SD: 1.7 +/- 1.6 mN/m to 24.3 +/- 6.7 mN/m, p = 0.0001) and only the addition of the PLA2 containing fraction from meconium to surfactant also significantly increased surface tension (mean 1.7 +/- 1.6 mN/m to 19.0 +/- 3.58 mN/m, p < 0.0001). Conclusion: PLA2 is present in meconium and inhibits the activity of pulmonary surfactant in vitro. Therefore, PLA2 in meconium may contribute to surfactant inactivation and alveolar atelectasis in MAS.     

Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs

We have created a totally synthetic, protein-free surfactant (Exosurf) composed of dipalmitoylphosphatidylcholine, hexadecanol, and tyloxapol. We studied the effects of endotracheal instillation of Exosurf on survival and pulmonary function of preterm lambs delivered at 131 to 133 days gestation (term 148 days). Exosurf treatment was compared with instillation of surface-active material prepared from lung lavages of adult sheep and with no instillation. Lambs were delivered by cesarean section, paralyzed, and mechanically ventilated. The Exosurf group survived longer (80% alive at 11 hours) than did the no instillation group (30% alive at 11 hours) (P less than 0.05). There were no statistically significant differences between the Exosurf and sheep surfactant groups. We conclude that Exosurf, a synthetic surfactant, produces significant improvement in survival and pulmonary function in preterm lambs.     

Different expression of surfactant protein B mature peptide and proprotein at 21 weeks'' gestation in human fetal pulmonary epithelial cells

AIM: The aim of this study is to evaluate the maturation of pulmonary epithelial cells in human fetal lungs at 21 weeks' gestation. METHODS: Eight fetuses at 21 weeks' gestation were evaluated. The maturation of pulmonary epithelial cells was assessed by immunohistochemical examination for surfactant proteins and by electron microscopy. RESULTS: Surfactant protein B mature peptide was detected slightly in the epithelial lining of the bronchioles, but was totally absent in the terminal airways. Surfactant protein B proprotein was clearly detected in the epithelial lining of both bronchioles and terminal airways. Transmission electron microscopy of terminal airway cells showed abundant glycogen granules and few intracellular organelles. CONCLUSIONS: The production of mature surfactant protein B in terminal airways is scarce at 21 weeks' gestation, which is associated with the immature mechanism of proprotein processing in the cytoplasm.     

肺表面活性物质蛋白 B、C 基因变异与蒙古族早产儿 呼吸窘迫综合征相关性研究

目的研究肺表面活性物质蛋白(SP)B、SP-C基因外显子4(exon4)区域基因变异与蒙古族早产儿呼吸窘迫综合征(RDS)的相关性。方法选择住院治疗的无血缘关系的蒙古族RDS早产儿50例(男31例,女19例),同期、同民族和同群体中无血缘关系的非RDS早产儿50例为对照组(男27例,女23例),分别用聚合酶链式反应(PCR)基因多态性分析和基因检测技术对SP-B、SP-C基因exon4区域基因进行测序,并比较两组患儿SP-B基因exon4区域1580位点基因变异及基因型频率、SP-C基因exon4区域c.571C A(T138N)位点基因变异及基因型频率的差异。结果检测出SP-B基因exon4区域1580位点基因变异,RDS组14例,变异率为28%,非RDS组11例,变异率为22%,两组差异无统计学意义(χ2=0.480,P 0.05)。RDS组1580位点CC、TT、CT基因型频率分别为16%、72%和12%,非RDS组则分别为10%、78%和12%;RDS组C等位基因频率为22%、T等位基因频率为78%,非RDS组则分别为16%、84%;两组间基因型频率差异无统计学意义(χ~2=1.170,P 0.05)。检测出SP-C基因exon 4区域c.571 C A(T 138 N)位点基因变异,RDS组41例,变异率为82%,非RDS组6例,变异率为12%,两组间差异有统计学意义(χ~2 =49.177,P 0.05)。RDS组c.571C A(T138N)位点CC、AA、AC三种基因型频率分别为18%、50%和32%,非RDS组分别为88%、8%和4%;RDS组C等位基因频率为34%、A等位基因频率为66%,非RDS组则分别为90%、10%,两组间A等位基因型频率的差异有统计学意义(χ~2=66.553,P 0.05)。结论携带SP-C基因exon 4区域c.571 C A(T 138 N)位点A等位基因的蒙古族早产儿患RDS的风险更高,而SP-B基因exon 4区域1580位点基因变异与蒙古族早产儿发生RDS无关。     

高频振荡通气、肺表面活性物质联合一氧化氮吸入治疗新生儿低氧性呼吸衰竭的临床研究

目的 探讨用高频振荡通气（HFOV）、肺表面活性物质（PS）联合一氧化氮吸入（iNO）治疗新生儿低氧性呼吸衰竭（HRF）的疗效。方法 116例HRF患儿随机分为三联组和二联组,各58例。三联组采用HFOV、PS联合iNO治疗;二联组采用HFOV 联合iNO治疗。观察两组患儿治疗前及治疗后24 h、48 h的血气分析、PaO2/FiO2（P/F）、OI值和肺动脉压力（PA）的变化,比较不同P/F值、OI值和是否合并PPHN患儿的治疗结局。结果 三联组的上机时间和iNO治疗时间均短于二联组（P<0.01）,且治疗后24 h、48 h的血气指标PaO2 、PaCO2均优于二联组（P<0.01）。三联组合并PPHN的患儿治疗后24 h、48 h的PA值均较二联组下降明显（P<0.01）。在P/F值≤50的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的P/F值均低于存活者（P<0.01）。在OI值≥40的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的OI值均高于存活者（P<0.01）。三联组合并PPHN患儿治愈率优于二联组（P<0.05）。三联组住院时间较二联组缩短（P<0.01）。三联组总治愈率高于二联组（P<0.05）。两组患儿并发症发生率比较差异无统计学意义（P >0.05）。治疗中两组均未监测到严重不良反应。结论 HFOV、PS和iNO三联治疗较HFOV和iNO二联治疗新生儿HRF更为有效,可显著改善氧合,提高患儿的存活率,尤其是为患严重肺部疾病合并PPHN,且P/F值≤50或OI值≥40的病情极危重患儿提供了一个新的治疗手段。     

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目的评估缺氧新生儿肺动脉高压(PAH)的发生及其对左室形态及功能的影响,探讨缺氧性PAH新生儿血浆脑利钠肽(BNP)水平与左室舒张功能的关系。方法选择2003年11月至2008年11月解放军总医院和北京军区总医院附属八一儿童医院新生儿重症监护室(NICU)收治的缺氧新生儿52例,根据彩色多普勒超声检查是否存在PAH分为PAH组(34例)与对照组(18例),比较2组患儿彩色多普勒超声心动图资料及其与左室舒张功能、血浆BNP水平的关系。结果(1)与对照组相比,PAH组左室舒张末内径(LVDd)、右室内径(RV)、肺动脉内径(PA)明显增大(P<0.05);三尖瓣反流峰值(VTR)流速增快及肺动脉收缩压(PASP)升高(P<0.05),室间隔增厚不明显(P>0.05)。(2)PAH组二尖瓣口血流多普勒频谱A峰流速(AV)、舒张早期充盈时间速度积分(AVTI)及A峰流速与E峰流速比值(AV/EV)、左房充盈分数(AVTI/EVTI)均较对照组显著增加(P<0.01);PAH组的左室等容舒张时间(LIVRT)延长,但与对照组相比差异无统计学意义(P>0.05),EV、舒张末期充盈时间速度积分(EVTI)及E峰减速时间(...