吸入性一氧化氮对全猪体外循环模型肺表面活性物质的影响

目的 :研究吸入性一氧化氮 (INO)是否能够改善心肺转流术 (CPB)后猪肺表面活性物质 (S)的生成和相关肺顺应性 ,并探讨机械通气下肺损伤机制。方法 :30头猪随机分为 6组 :假手术组 (Sham ,n =5 ) ,Sham +INO(n=5 ) ,CPB(n =5 ) ,CPB +INO(n =5 ) ,CPB +脂多糖 (LPS ,n =5 ) ,CPB +LPS +INO (n =5 )。麻醉诱导完成后 ,将INO(质量分数为 2 0× 10 -6)添加到混合气体中 ,给猪吸入直至实验结束。在INO治疗 2h后 ,采集支气管 肺泡洗出液 (BAL)进行S分析和细胞学检查。另外 ,测定肺血流动力学参数和肺顺应性。首次采样后 (T0 )实施CPB ,持续 90min。CPB后 4h(T4)和 2 4h(T2 4) ,重复BAL和其它测定。CPB后 90min内 ,输注LPS(4 μg·kg-1)给特定组以便刺激炎性反应。结果 :INO组猪肺血流动力学参数 (肺动脉压、肺血管阻力指数和氧合指数 )在T4和T2 4明显优于对照组。然而 ,各组猪的肺顺应性均随时间呈递减性降低 ,同T0 相比 ,在T2 4呈现显著性下降。与对照组相比 ,INO预治疗组猪的S亚活性成分———大聚体 (LA)含量在T0 明显增加 ,但在T2 4,所有组LA和总S含量均明显下降 ,其中LPS组LA含量在T4后即明显降低。BAL中的总细胞计数以及中性粒细胞分类均随时间而增加 ,INO组略低于其它组。结论 :INO吸入对猪S (LA)的影

Influence of inhaled nitric oxide on surfactant in the total cardiopulmonary bypass pig model

OBJECTIVE: To study whether or not inhaled nitric oxide (INO) can improve surfactant production and pulmonary mechanics after CPB in pigs, and to seek the mechanism of lung injury during mechanical ventilation. METHODS: Thirty pigs were randomized into 6 groups: Sham (n = 5), Sham + INO (n = 5), CPB (n = 5), CPB + INO (n = 5), CPB + lipopolysaccharide (LPS) (n = 5), and CPB + LPS + INO (n = 5). After anesthesia induction, INO (mass fraction, 20 x 10(-6)), added to the gas mixture, was given to the animals throughout the procedure. After 2 hours of INO treatment, broncho-alveolar lavage (BAL) fluid was taken for surfactant assay and cytology analysis. Pulmonary hemodynamics parameters and lung compliance were measured as well. CPB was performed for 90 minutes after the first BAL sampling at T0. Four hours (T4) and 24 hours (T24) following CPB, BAL and other measurements were repeated. After CPB, LPS (4 micrograms.kg-1) was infused to specific groups of pigs within 90 minutes in order to stimulate the inflammation process. RESULTS: Pulmonary hemodynamics parameters (pulmonary artery pressure, pulmonary vascular resistance and oxygenation) in all INO groups were much better than those of the control groups at T4 and T24. However, lung compliance of pigs in all groups declined with time, and showed statistically significant differences at T24 compared with T0. At T0, the active subfraction of surfactant (large aggregate, LA) was increased in animals given INO treatment compared with the controls, but decreased with time, and at T24 significantly reduced in all groups. In LPS groups, this decrease LA after T4 was very obvious. Total cell counts and the percent differentials of neutrophils in BAL increased with time, being lower in the INO groups than in other groups. CONCLUSION: INO exposure exerted time-related effects on the lung surfactant (LA). Initially, INO resulted in short-term increase of surfactant production at T0. However, with time passing by, INO exposure following CPB did not prevent long-term decrease of lung surfactant and lung compliance although INO was beneficial for pulmonary hemodynamics and oxygenation. In summary, despite the use of INO, synergetic effects of long-term hyperoxia, mechanical ventilation and inflammation following CPB may exacerbate pulmonary mechanics and result in surfactant dysfunction.