Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury
Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury
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DOI：
10.1164/rccm.200302-305oc
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发表时间：
2005-01-15
影响因子：
24.7
通讯作者：
Freeman, BA
中科院分区：
文献类型：
--
作者：
Lang, JD;Figueroa, M;Freeman, BA
认识到CO2改变了一氧化氮（NO）衍生的炎症氧化剂的化学反应性，我们研究了高碳酸血症是否会调节肺部炎症反应。家兔（n = 72）以约7 ml/kg潮气量通气6小时。将动物随机分配至以下条件之一：正常碳酸血症（Pa-CO2，约35-40 mm Hg）、正常碳酸血症+脂多糖（LPS）、正常碳酸血症+ LPS +吸入NO（iNO，约20 ppm）、高碳酸血症（Pa-CO2，约60 mm Hg）、高碳酸血症+ LPS和高碳酸血症+ LPS + iNO。高碳酸血症+ LPS组与暴露于正常碳酸血症+ LPS组相比，支气管肺泡灌洗液蛋白浓度（p < 0.05）、肺湿干比（p < 0.05）、支气管肺泡灌洗液细胞计数（p < 0.05）和肺组织学改变显著增加，与更严重的损伤一致。此外，在高碳酸血症+ LPS条件下，诱导型一氧化氮合酶的表达（p <0.05）、组织髓过氧化物酶含量（p < 0.05）和肺蛋白3-硝基酪氨酸衍生物的形成（p < 0.05）最大。暴露于无LPS的高碳酸血症条件下的组没有表现出这些变化。吸入iNO减弱了肺损伤的选定指标。我们的结论是，通过降低速率和潮气量诱导的高碳酸血症放大了肺部炎症反应。
Appreciating that CO2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n = 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa-CO2 at approximately 35-40 mm Hg), eucapnia + lipopolysaccharide (LPS), eucapnia + LPS + inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa-CO2 at approximately 60 mm Hg), hypercapnia + LPS, and hypercapnia + LPS + iNO. The hypercapnia + LPS groups compared with groups exposed to eucapnia + LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p < 0.05), lung wet-to-dry ratios (p < 0.05), bronchoalveolar lavage fluid cell counts (p < 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p < 0.05), tissue myeloperoxidase content (p < 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p < 0.05) was greatest under conditions of hypercapnia + LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes. The inhalation of iNO attenuated selected indices of lung injury. We conclude that hypercapnia induced by means of reduced rate and tidal volume amplifies pulmonary inflammatory responses.