Zhou Z H, Sun B, Lin K, Zhu L W
Children's Hospital Research Institute, Shanghai Medical University, Shanghai, Peoples Republic of China.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):581-8. doi: 10.1164/ajrccm.161.2.9901048.
Improvement of pulmonary perfusion and blood oxygenation and prevention of acute lung injury (ALI) may rely on ventilation strategy. We hypothesized that application of a combined surfactant, inhaled nitric oxide (iNO), and pressure support ventilation (PSV) should more effectively protect the lungs from injury. Anesthetized and intubated adult rabbits weighing 2.8 +/- 0.3 kg were allowed to breathe room air while receiving oleic acid intravenously (60 microl/kg). Within 90 min this caused a reduction of Pa(O(2)) from 94 +/- 7 to 48 +/- 3 mm Hg and dynamic lung compliance (Cdyn) from 1.59 +/- 0.22 to 0.85 +/- 0.10 ml/cm H(2)O/kg (both p < 0.01), and increase of intrapulmonary shunting (Q S/Q T) from 9.4 +/- 1.2 to 27 +/- 5% (p < 0.05). PSV was subsequently applied with 3 cm H(2)O of continuous positive airway pressure and FI(O(2)) of 0.3, and the animals were randomly allocated to four groups, receiving: (1) PSV only (Control, n = 10); (2) iNO at 20 ppm (NO, n = 9); (3) surfactant phospholipids at 100 mg/kg (Surf, n = 8); and (4) surfactant at 100 mg/kg and iNO at 20 ppm (SNO, n = 8). PSV level was varied to maintain a tidal volume of 8 to 10 ml/kg for another 12 h or until early animal death. Five animals in the SNO, three each in the NO and Surf group, and one in the Control group survived 12 h (SNO versus Control, p < 0.05). The NO, Surf, and SNO groups had significantly improved mean Pa(O(2)) (> 70 mm Hg, p < 0.05), and reduced Q S/Q T (15, 19, and 17%, respectively, p < 0.05) at 6 and 12 h, but not in the Control group. The SNO group had the highest values of Cdyn at 12 h, alveolar aeration and disaturated phosphatidylcholine-to-total protein ratio in bronchoalveolar lavage fluid, and the lowest wet-to-dry lung weight ratio and lung injury score (p < 0.05). The results indicate that early alleviation of ALI by surfactant, iNO, and PSV is due to synergistic effects, and only PSV in this model had limited effects.
肺灌注和血液氧合的改善以及急性肺损伤（ALI）的预防可能依赖于通气策略。我们假设联合应用表面活性剂、吸入一氧化氮（iNO）和压力支持通气（PSV）能更有效地保护肺免受损伤。将体重2.8±0.3 kg的成年麻醉插管兔在静脉注射油酸（60微升/千克）时给予室内空气呼吸。在90分钟内，这导致动脉血氧分压（Pa(O₂)）从94±7降至48±3毫米汞柱，动态肺顺应性（Cdyn）从1.59±0.22降至0.85±0.10毫升/厘米水柱/千克（均p<0.01），肺内分流（Q S/Q T）从9.4±1.2增加至27±5%（p<0.05）。随后应用PSV，持续气道正压为3厘米水柱，吸入氧分数（FI(O₂)）为0.3，动物被随机分为四组，分别接受：（1）仅PSV（对照组，n = 10）；（2）20 ppm的iNO（NO组，n = 9）；（3）100毫克/千克的表面活性剂磷脂（Surf组，n = 8）；（4）100毫克/千克的表面活性剂和20 ppm的iNO（SNO组，n = 8）。PSV水平进行调整以维持潮气量为8至10毫升/千克，持续12小时或直至动物早期死亡。SNO组有5只动物、NO组和Surf组各有3只动物以及对照组有1只动物存活12小时（SNO组与对照组相比，p<0.05）。在6小时和12小时时，NO组、Surf组和SNO组的平均Pa(O₂)显著改善（>70毫米汞柱，p<0.05），Q S/Q T降低（分别为15%、19%和17%，p<0.05），但对照组未改善。SNO组在12小时时Cdyn值最高，支气管肺泡灌洗液中的肺泡通气、不饱和磷脂酰胆碱与总蛋白比值最高，湿干肺重量比和肺损伤评分最低（p<0.05）。结果表明，表面活性剂、iNO和PSV对ALI的早期缓解是由于协同作用，在该模型中仅PSV的作用有限。
