Regional Lung Function in Acute Lung Injury

急性肺损伤时的局部肺功能

• 批准号: 7682971
• 负责人: Guido Musch
• 金额: $ 13.07万
• 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 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682971
• 关键词: Acute Lung Injury; Address; Adult Respiratory Distress Syndrome; Advisory Committees; Affect; Alveolar; Alveolus; Anesthesia procedures; Animal Model; Atelectasis; Attenuated; Characteristics; Complement; Complement component C4; Critical Care; Data; Defect; Development; Diffuse; Edema; Educational Curriculum; Environmental air flow; Equilibrium; Experimental Models; Functional Imaging; Functional disorder; Gases; General Hospitals; Health Care Costs; Human; Image; Impairment; Inflammation; Inflammation Mediators; Inflammatory; Injury; Intervention; Investigation; Lead; Leukotrienes; Lung; Massachusetts; Mechanical ventilation; Mediating; Metabolic; Methods; Modeling; Molecular; Morbidity - disease rate; Neutrophil Activation; Nitrogen; Pathogenesis; Patients; Perfusion; Physicians; Physiological; Positive-Pressure Respiration; Positron-Emission Tomography; Process; Recruitment Activity; Regional Perfusion; Research; Research Design; Research Personnel; Research Project Grants; Respiratory physiology; Scientist; Shunt Device; Structure; Structure of parenchyma of lung; Syndrome; Testing; Time; Training; Ventilator-induced lung injury; Work; X-Ray Computed Tomography; base; career; density; experience; fluorodeoxyglucose; improved; in vivo; indexing; injured; innovation; insight; intervention effect; knowledge base; lung injury; mortality; neutrophil; prevent; programs; response; tool

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 (ALl). His long-term objective is to further the understanding of the pathophysiology of the impairment of gas exchange in ALl 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 ALl 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 ALl: 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 ALl; 2) To identify the mechanisms by which recruiting strategies affect regional gas exchange in patients with ALl 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; and 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 ALl 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 [lSF]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.

候选人接受过重症监护和麻醉方面的培训，并具有气体研究背景 急性肺损伤（ALl）中的交换和机械通气。他的长期目标是加深对 ALl 中气体交换受损的病理生理学以及机械性损伤的机制 通气影响气体交换和肺损伤的进展。在此应用中，他建议使用创新的 基于正电子发射断层扫描 (PET) 功能成像的生理研究工具，用于测试 以下假设：1) AL1 中气体交换受损是局部肺功能改变的结果， 涉及区域灌注和区域通气； 2) 肺泡复张策略，例如呼气末正压 压力和复张策略对 AL1 具有两个主要作用：a) 恢复非通气区域的通气或 b) 过度扩张已经通气的区域，并将肺灌注转移至非通气区域。 平衡 这两种效应之间决定了它们对气体交换的净效应； 3）招聘与招聘之间的平衡 过度扩张还决定了募集策略是减弱还是促进相关的炎症过程 呼吸机引起的肺损伤 (VILI)。为了检验这些假设，候选人建议采取以下措施 具体目标 (SA)：1) 描述 AL1 患者的局部气体交换特征； 2) 识别机制 哪些肺复张策略会影响 AL1 患者和特征明确的肺损伤患者的局部气体交换 具有不同招聘潜力的模特； 3）确定招募策略是否能够调节 与 VILI 相关的炎症过程取决于潜在的募集潜力； 4) 测试 白三烯是否介导有害通气策略导致中性粒细胞激活并导致中性粒细胞活化的过程 与 VILI 相关的炎症级联反应。研究设计包括针对 AL1 患者的研究，以解决 SA1 和 SA2，以及肺损伤实验模型的研究，以补充 SA2 的患者数据并解决 SA3 和 SA4。该方法利用静脉注射[13N]氮气的 PET 成像来评估区域灌注， 区域分流和区域通气，以及[lSF]氟脱氧葡萄糖以评估区域中性粒细胞代谢活动， 细胞炎症的指标。该项目与健康的相关性在于它有可能提供重要的新成果 深入了解具有高发病率、死亡率和相关医疗费用的综合征的病理生理学。 为了有效掌握拟议的研究并优化教育体验，候选人将受到以下指导： 由医师科学家和具有不同背景的科学家组成的咨询委员会，他们将提供生理、 形态学和方法论的洞察力。该研究项目将在麻省总医院进行 并将辅之以生理调查方面的结构化教育课程，该课程将提供 候选人拥有完成该项目和在其研究生涯中取得进步所需的知识基础。