Regional Lung Function in Acute Lung Injury

急性肺损伤时的局部肺功能

• 批准号: 7123884
• 负责人: Guido Musch
• 金额: $ 13.31万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-19 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123884
• 关键词: adult respiratory distress syndrome; bioimaging /biomedical imaging; clinical research; disease /disorder model; human subject; iatrogenic disease; inflammation; laboratory mouse; leukocyte activation /transformation; leukotrienes; lung imaging /visualization /scanning; lung injury; neutrophil; pathologic process; positive pressure breathing; positron emission tomography; respirators; respiratory airflow measurement; respiratory function; respiratory gas transport; sheep

DESCRIPTION (provided by applicant): The candidate is trained in Critical Care and Anesthesia and has a research background in the study of gas exchange and mechanical ventilation in Acute Lung Injury (ALI). His long-term objective is to further the understanding of the pathophysiology of the impairment of gas exchange in ALI and of the mechanisms by which mechanical ventilation affects gas exchange and the progression of lung injury. In this application he proposes to use innovative tools of physiologic investigation based on functional imaging with Positron Emission Tomography (PET) to test the following hypotheses: 1) The impairment of gas exchange in ALI is the result of alterations of regional lung function that involve both regional perfusion and regional aeration; 2) Alveolar recruiting strategies, such as Positive End-Expiratory Pressure and Recruitment Maneuvers, can have two main effects in ALI: a) restore aeration to non-aerated regions or b) overexpand regions that are already aerated and shift pulmonary perfusion toward non-aerated regions. The balance between these two effects determines their net effect on gas exchange; 3) The balance between recruitment and overexpansion also determines whether recruiting strategies attenuate or promote the inflammatory process associated with Ventilator-Induced Lung Injury (VILI). To test these hypotheses the candidate proposes to pursue the following specific aims (SA): 1) To characterize regional gas exchange in patients with ALI; 2) To identify the mechanisms by which recruiting strategies affect regional gas exchange in patients with ALI and in well-characterized lung injury models with different potential for recruitment; 3) To determine whether the ability of recruiting strategies to modulate the inflammatory process associated with VILI depends on the underlying potential for recruitment; 4) To test whether leukotrienes mediate the process by which injurious ventilatory strategies lead to neutrophil activation and to the inflammatory cascade associated with VILI. The research design includes studies in patients with ALI to address SA1 and SA2, and studies in experimental models of lung injury to complement the patient data for SA2 and to address SA3 and SA4. The methods utilize PET imaging of intravenously injected [13N]nitrogen to assess regional perfusion, regional shunt and regional ventilation, and of [18F]fluorodeoxyglucose to assess regional neutrophil metabolic activity, an index of cellular inflammation. The health-relatedness of the project is in its potential to provide significant new insight into the pathophysiology of a syndrome with high morbidity, mortality and associated healthcare costs. To effectively master the proposed research and optimize the educational experience, the candidate will be guided by an advisory committee of physician-scientists and scientists with diverse background, who will provide physiological, morphological and methodological insight. The research project will be carried out at Massachusetts General Hospital and will be complemented by a structured educational curriculum in physiologic investigation that will provide the candidate with the knowledge base that is necessary to accomplish this project and to progress in his research career. (End of Abstract)

描述（由申请人提供）： 候选人接受了重症监护和麻醉的培训，并在急性肺损伤（ALI）的气体交换和机械通气研究方面具有研究背景。 他的长期目标是进一步理解ALI气体交换损害的病理生理学以及机械通气影响气体交换和肺损伤进展的机制。 在此应用中，他提议使用基于正电子发射断层扫描（PET）功能成像的生理研究的创新工具来检验以下假设：1）ALI中气体交换的损害是涉及区域灌注和区域灌注和法规充气的区域肺功能改变的结果； 2）肺泡募集策略，例如正气压力和招募动作，在ALI中可以产生两个主要影响：a）恢复到非平均地区的充气或b）已经充气并将肺部灌注转向非aerated区域的过度膨胀区域。 这两个效果之间的平衡决定了它们对气体交换的净影响； 3）招募与过度膨胀之间的平衡还决定了招募策略是减弱还是促进与呼吸机诱导的肺损伤相关的炎症过程（VILI）。 为了检验这些假设，候选人建议追求以下特定目标（SA）：1），以表征ALI患者的区域气体交换； 2）确定招聘策略影响ALI患者和特征良好的肺损伤模型的区域气体交换的机制，具有不同的招募潜力； 3）确定招聘策略调节与VILI相关的炎症过程的能力是否取决于招募的潜在潜力； 4）测试白细胞是否介导了造成损害的通气策略导致嗜中性粒细胞激活和与Vili相关的炎症级联反应的过程。 研究设计包括对ALI患者的研究，以解决SA1和SA2，以及在肺损伤实验模型中的研究，以补充SA2的患者数据并解决SA3和SA4。 这些方法利用静脉注射的[13N]氮的PET成像评估区域灌注，区域分流和区域通风，以及[18F]氟脱氧氧化葡萄糖来评估中性粒细胞代谢活性，这是细胞炎症的指数。 该项目的健康相关性旨在为具有高发病率，死亡率和相关医疗费用的综合征的病理生理学提供重大新见解。 为了有效地掌握拟议的研究并优化教育经验，候选人将由具有不同背景的医师科学家和科学家的咨询委员会指导，他们将提供生理，形态学和方法论洞察力。 该研究项目将在马萨诸塞州综合医院进行，并在生理调查中进行结构化的教育课程补充，该课程将为候选人提供实现该项目并在其研究生涯中进步所必需的知识库。 （抽象的结尾）