Zhu G F, Sun B, Niu S F, Cai Y Y, Lin K, Lindwall R, Robertson B
Children's Hospital Research Institute; Department of Pulmonology, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.
Am J Respir Crit Care Med. 1998 Aug;158(2):437-43. doi: 10.1164/ajrccm.158.2.9711107.
Intratracheal administration of surfactant and inhaled nitric oxide (INO) have had variable effects in clinical trials on patients with acute respiratory distress syndrome (ARDS). We hypothesized that combined treatment with exogenous surfactant and INO may have effects in experimental ARDS. After intravenous infusion of oleic acid in adult rabbits and 4-6 h of ventilation, there was more than a 40% reduction in both dynamic compliance (Cdyn) of the respiratory system and functional residual capacity (FRC), a 50% increment of respiratory resistance (Rrs), a 70% reduction in PaO2 /FIO2, and an increase in intrapulmonary shunting (Q S/Q T) from 4.4 to 33.5%. The animals were then allocated to groups receiving (1) neither surfactant nor INO (control), (2) 100 mg/kg of surfactant (S) administered intratracheally, (3) 20 ppm INO (NO), or (4) 100 mg/kg of surfactant and 20 ppm INO (SNO), and subsequently ventilated for 6 h. After the period of ventilation, the animal lungs were used for analysis of disaturated phosphatidylcholine (DSPC) and total proteins (TP) in bronchoalveolar lavage fluid (BALF), and for determination of alveolar volume density (VV). The animals in the control group had the lowest survival rate, and no improvement in lung mechanics and blood oxygenation, whereas those in the S group had a modest but statistically significant improvement in Cdyn, Rrs, PaO2 and FRC, reduced Q S/Q T, lowered minimum surface tension (gammamin) of BALF, and increased DSPC/ TP and alveolar VV. The NO group had increased PaO2 and reduced Q S/Q T. The SNO group showed improved Cdyn, Rrs, FRC, DSPC/TP, alveolar VV, and gammamin of BALF comparable to the S group, but there was a further increase in survival rate and PaO2, and additional reduction in Q S/Q T and TP in BALF. These results indicate that, in this animal model of ARDS, a combination of surfactant therapy and INO is more effective than either treatment alone.
在急性呼吸窘迫综合征（ARDS）患者的临床试验中，气管内给予表面活性剂和吸入一氧化氮（INO）产生了不同的效果。我们推测，外源性表面活性剂与INO联合治疗可能对实验性ARDS有效。成年兔静脉输注油酸并通气4 - 6小时后，呼吸系统的动态顺应性（Cdyn）和功能残气量（FRC）均降低了40%以上，呼吸阻力（Rrs）增加了50%，动脉血氧分压/吸入氧分数值（PaO2 /FIO2）降低了70%，肺内分流（QS/QT）从4.4%增加到33.5%。然后将动物分为四组，分别接受：（1）既不给予表面活性剂也不给予INO（对照组）；（2）气管内给予100 mg/kg表面活性剂（S组）；（3）20 ppm INO（NO组）；（4）100 mg/kg表面活性剂和20 ppm INO（SNO组），随后通气6小时。通气结束后，取动物肺组织用于分析支气管肺泡灌洗液（BALF）中的二饱和磷脂酰胆碱（DSPC）和总蛋白（TP），并测定肺泡容积密度（VV）。对照组动物的存活率最低，肺力学和血液氧合无改善，而S组动物的Cdyn、Rrs、PaO2和FRC有适度但具有统计学意义的改善，QS/QT降低，BALF的最小表面张力（γmin）降低，DSPC/TP和肺泡VV增加。NO组动物的PaO2升高，QS/QT降低。SNO组动物的Cdyn、Rrs、FRC、DSPC/TP、肺泡VV和BALF的γmin与S组相当，但存活率和PaO2进一步升高，BALF中的QS/QT和TP进一步降低。这些结果表明，在这个ARDS动物模型中，表面活性剂治疗与INO联合使用比单独使用任何一种治疗方法都更有效。
