Lin Shu-Min, Lin Horng-Chyuan, Lee Kang-Yun, Huang Chien-Da, Liu Chien-Ying, Wang Chun-Hua, Kuo Han-Pin
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan.
Shock. 2007 Oct;28(4):453-60. doi: 10.1097/shk.0b013e3180487fb5.
Mechanical ventilators are commonly used to support critically ill patients; however, inappropriate ventilator settings might initiate or augment lung injury. To determine whether a large tidal volume (Vt) augments inflammatory responses and neutrophil sequestration in the lungs of rats receiving intratracheal lipopolysaccharides (LPS). Rats received intratracheal instillation of LPS (0.5 mg/kg) followed by 4 h of mechanical ventilation (MV) at 60 strokes per min with a Vt of 10 mL/kg as control MV, or 30 strokes per min with a Vt of 20 mL/kg of body weight as high-volume MV (HMV). In addition, monoclonal antibodies against rat intercellular adhesion molecule 1 (ICAM-1) or immunoglobulin G (50 mg/kg) were administered 30 min before LPS instillation and MV. Our study demonstrates that HMV enhances pulmonary permeability and induces neutrophil recruitment into the alveolar space and pulmonary edema. Intratracheal instillation of LPS caused marked lung injury, neutrophil recruitment, and production of cytokines and chemokines. Combining LPS instillation and HMV synergistically upregulated interleukin 1beta (IL-1beta) production and neutrophil sequestration in lung tissues. The ICAM-1 expression in lung tissues was responsible for the synergistic effects of neutrophil sequestration. Synergistic upregulation of IL-1beta production and neutrophil sequestration was attenuated by blocking ICAM-1 by neutralizing antibody pretreatment. High Vt MV in LPS-injured lung causes synergistic production of IL-1beta and sequestration of neutrophil via ICAM-1-dependent effects.
机械通气常用于支持重症患者；然而，不恰当的通气设置可能引发或加重肺损伤。为了确定大潮气量（Vt）是否会增强接受气管内注射脂多糖（LPS）的大鼠肺部的炎症反应和中性粒细胞滞留。大鼠接受气管内注射LPS（0.5 mg/kg），随后以每分钟60次呼吸频率进行4小时机械通气（MV），Vt为10 mL/kg作为对照MV，或以每分钟30次呼吸频率，Vt为20 mL/kg体重作为大潮气量MV（HMV）。此外，在注射LPS和进行MV前30分钟给予抗大鼠细胞间黏附分子1（ICAM-1）单克隆抗体或免疫球蛋白G（50 mg/kg）。我们的研究表明，HMV会增强肺通透性，诱导中性粒细胞募集到肺泡腔并导致肺水肿。气管内注射LPS会引起明显的肺损伤、中性粒细胞募集以及细胞因子和趋化因子的产生。联合注射LPS和HMV会协同上调白细胞介素1β（IL-1β）的产生以及肺组织中的中性粒细胞滞留。肺组织中ICAM-1的表达是中性粒细胞滞留协同效应的原因。通过中和抗体预处理阻断ICAM-1可减弱IL-1β产生和中性粒细胞滞留的协同上调。LPS损伤的肺中高Vt MV通过ICAM-1依赖性效应导致IL-1β的协同产生和中性粒细胞的滞留。
