Ventilator-Induced Lung Injury:Mechanisms & Consequences

呼吸机引起的肺损伤：机制

• 批准号: 6898699
• 负责人: SCOTT E SINCLAIR
• 金额: $ 12.85万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898699
• 关键词: albumins; breath tests; cell type; diagnostic respiratory lavage; enzyme linked immunosorbent assay; hypercapnia; iatrogenic disease; immunocytochemistry; inflammation; interleukin 8; laboratory rabbit; lung injury; myeloperoxidase; oximetry; posture; radioactive microsphere technique; respirators; respiratory airflow disorder; thermogravimetry; tumor necrosis factor alpha; vasoconstriction

Mechanical ventilation is an important tool in the management of respiratory failure. However, the ventilation strategy can initiate or exacerbate lung injury. Several mechanisms have been implicated in ventilator-induced lung injury (VILI), particularly cyclical airway collapse and reopening. Inferential data supports cyclical airway collapse as an important factor in the genesis of VILI, but it has never been definitively documented. Strategies minimizing alveolar over distension and cyclical airway closure decrease mortality in ARDS patients but are confounded by hypercapnic acidosis, itself a potential modulator of lung injury. Establishing the presence of cyclical airway collapse, its abolition with palliative interventions, and correlation with severity and distribution of injury is vital to understanding VILI and developing relevant strategies to prevent it. This proposal will evaluate mechanisms by which mechanical ventilation induces lung injury and initiates inflammation in a rabbit model of VILI caused solely by mechanical forces. I will address the following questions: 1) Is cyclical airway collapse and reopening a stimulus for inflammation? 2) Where in the lung and on which cell types do mechanical forces exert their effects? 3) Can we definitively document cyclical airway closure? 4) If so, can we accurately predict ventilatory conditions that prevent it? 5) Do non- mechanical forces (hypercapnia) play a protective role in VILI? Methods: Spatial inflammation distribution measured with monoclonal antibody ELISA and immunohistochemistry. Spatial injury measured by extravascular albumin accumulation and gravimetrics. Regional V and Q measured with aerosolized and perfused fluorescent microspheres. Global gas exchange measured with the multiple inert gas elimination technique. Ventilation heterogeneity measured with multiple breath nitrogen washout. Aim 1A: Examine how posture change and PEEP effect severity and distribution of injury and inflammation. Aim 1B: Determine the anatomical location and cell type(s) responsible inflammation in VILI. Aim 2A : Measure effects of hypercapnia on lung injury and inflammation during VILI. Aim 2B: Examine how hypercapnia alters hypoxic pulmonary vasoconstriction and reduces VILI. Aim 2C : Examine how hypercapnia effects ventilation heterogeneity and reduces VILI. Aim 3A: Document cyclical airway collapse and reopening via changes in regional ventilation distribution. Aim 3B: Validate a method to estimate appropriate PEEP level to prevent cyclical airway collapse.

机械通气是管理呼吸衰竭的重要工具。但是，通风策略可以引发或加剧肺损伤。几种机制与呼吸机诱导的肺损伤（VILI）有关，尤其是周期性气道塌陷和重新开放。推论数据支持周期性气道崩溃，这是VILI起源的重要因素，但从未有过证实。策略最小化肺泡在延伸和周期性气道闭合降低了ARDS患者中的死亡率，但被高含量酸中毒所困扰，这本身就是肺损伤的潜在调节剂。建立周期性气道崩溃的存在，对姑息干预措施的废除以及与严重性和伤害分布的相关性对于理解VILI和制定相关策略以防止损伤至关重要。该提案将评估机械通气诱导肺损伤并引发炎症的机制，并在仅由机械力引起的VILI兔模型中引起炎症。我将解决以下问题：1）周期性气道崩溃并重新打开炎症的刺激吗？ 2）在肺中以及哪种细胞类型在哪里发挥作用？ 3）我们可以明确记录周期性气道关闭吗？ 4）如果是这样，我们是否可以准确预测预防它的通气条件？ 5）非机械力（HyperCapnia）在Vili中起保护作用吗？方法：用单克隆抗体ELISA和免疫组织化学测量的空间炎症分布。通过血管外白蛋白的积累和重力测量的空间损伤。用雾化和灌注荧光微球测量的区域V和Q。通过多重惰性气体消除技术测量的全球气体交换。通气异质性通过多次呼吸氮冲洗测量。 AIM 1A：检查姿势变化和窥视如何影响严重程度以及损伤和炎症的分布。 AIM 1B：确定VILI中的解剖位置和细胞类型。 AIM 2A：测量高碳酸盐对VILI期间肺损伤和炎症的影响。 AIM 2B：检查高碳酸脂蛋白如何改变低氧肺血管收缩并减少VILI。 AIM 2C：检查高碳水化合物如何影响通气异质性并减少VILI。 AIM 3A：通过区域通风分布的变化，可以记录周期性气道崩溃并重新开放。 AIM 3B：验证一种估计适当窥视水平的方法，以防止周期性气道崩溃。

项目成果

Therapeutic hypercapnia and ventilation-perfusion matching in acute lung injury: low minute ventilation vs inspired CO2.

• DOI: 10.1378/chest.130.1.85
• 发表时间: 2006-07
• 期刊: Chest
• 影响因子: 9.6
• 作者: S. Sinclair;D. Kregenow;I. Starr;C. Schimmel;W. Lamm;M. Hlastala;E. Swenson

Spatial distribution of sequential ventilation during mechanical ventilation of the uninjured lung: an argument for cyclical airway collapse and expansion.

未受伤肺机械通气期间顺序通气的空间分布：周期性气道塌陷和扩张的争论。

• DOI: 10.1186/1471-2466-10-25
• 发表时间: 2010
• 期刊: BMC pulmonary medicine
• 影响因子: 3.1
• 作者: Sinclair,ScottE;Polissar,NayakL;Altemeier,WilliamA
• 通讯作者: Altemeier,WilliamA

Positive end-expiratory pressure alters the severity and spatial heterogeneity of ventilator-induced lung injury: an argument for cyclical airway collapse.

• DOI: 10.1016/j.jcrc.2008.04.005
• 发表时间: 2009-06
• 期刊: JOURNAL OF CRITICAL CARE
• 影响因子: 3.7
• 作者: Sinclair, Scott E.;Chi, Emil;Lin, Hen-I;Altemeier, William A.
• 通讯作者: Altemeier, William A.