Regional Lung Function in Acute Lung Injury

急性肺损伤时的局部肺功能

• 批准号: 7491747
• 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/7491747
• 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; Effectiveness of Interventions; Environmental air flow; Equilibrium; Experimental Models; Functional Imaging; Functional disorder; Gases; General Hospitals; Health Care Costs; Human; Image; Impairment; Inflammation; Inflammatory; Injury; Intervention; Investigation; Lead; Leukotrienes; Lung; Massachusetts; Mechanical ventilation; Mediating; Mediator of activation protein; 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; Thinking; Time; Training; Ventilator-induced lung injury; Work; X-Ray Computed Tomography; base; career; density; experience; fluorodeoxyglucose; improved; in vivo; indexing; injured; innovation; insight; 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.

候选人接受了重症监护和麻醉的培训，并在气体研究中具有研究背景 急性肺损伤中的交换和机械通气（全部）。他的长期目标是进一步理解 在所有机理中，气体交换受损的病理生理学 通风会影响气体交换和肺损伤的进展。在此应用程序中，他提出使用创新 基于正电子发射断层扫描（PET）基于功能成像的生理研究工具，以测试 以下假设：1）全部气体交换的损害是区域肺功能改变的结果 涉及区域灌注和区域曝气； 2）肺泡招募策略，例如阳性呼吸器 压力和招聘操作可以总共有两个主要影响：a）恢复到非航空区域或 b）已经被充气并将肺部灌注转移到非平均区域的过度膨胀区域�平衡 在这两种效果之间决定了它们对气体交换的净影响； 3）招聘与 过度膨胀还确定招聘策略是减弱还是促进相关的炎症过程 呼吸机诱导肺损伤（VILI）。为了检验这些假设，候选人提出的提议 具体目的（SA）：1）表征所有患者的区域气体交换； 2）通过 哪种招募策略会影响所有和特征良好的肺损伤患者的区域气体交换 招聘潜力不同的模型； 3）确定招聘策略调制的能力是否 与VILI相关的炎症过程取决于招募的潜在潜力。 4）测试 白细胞是否介导受伤的通气策略导致中性粒细胞激活和 与VILI相关的炎症级联。研究设计包括对所有患者的研究 SA1和SA2，以及在肺损伤实验模型中的研究，以完成SA2的患者数据并解决 SA3和SA4。这些方法利用静脉注射[13n]氮的PET成像评估区域灌注， 区域分流和区域通风，以及[LSF]氟脱氧葡萄糖，以评估中性粒细胞代谢活性 细胞炎症指数。该项目的健康相关性有可能提供重要的新 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。 为了有效地掌握拟议的研究并优化教育经验，候选人将受到指导 具有潜水员背景的身体科学家和科学家的咨询委员会，他们将提供生理学， 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 并将由生理研究中的结构化教育课程完成，该课程将提供 拥有知识库的候选人是完成该项目并在其研究生涯中进步所必需的。