Assessment of lung function in small animals

小动物肺功能评估

• 批准号: 7390672
• 负责人: RAHIM R RIZI
• 金额: $ 39.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390672
• 关键词: Address; Air; Alveolar; Alveolar wall; Animal Model; Animals; Blood capillaries; Cell Death; Characteristics; Chronic; Classification; Clinical; Data; Deterioration; Diffusion; Disease; Disease Management; Disease Progression; Disease model; Early Diagnosis; Elastases; Endothelium; Environmental air flow; Equilibrium; Evolution; Exercise Tolerance; Exhalation; Exposure to; Functional disorder; Funding; Gases; Gold; Grant; Histology; Hour; Human; Hypoxia; Image; Inflammation; Inflammatory; Invasive; Investigation; Light; Lobar; Longitudinal Studies; Lung; Lung diseases; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Mediator of activation protein; Methods; Metric; Microscopic; Microspheres; Modeling; Modification; Molecular; Nature; Noble Gases; Oxygen measurement, partial pressure, arterial; Pancreatic Elastase; Pathogenesis; Pattern; Perfusion; Physiological; Plant Roots; Process; Protocols documentation; Pulmonary Emphysema; Pulmonary Hypertension; Pulmonary Ventilation; Pulmonary function tests; Pulmonology; Rattus; Reproducibility; Research; Research Personnel; Respiratory physiology; SU 5416; Smoking; Spin Labels; Sprague-Dawley Rats; Staging; Standards of Weights and Measures; Structure; Sum; Techniques; Tidal Volume; Time; Tissues; Today; Tracer; Uncertainty; Validation; Vascular Endothelial Growth Factors; Week; Whole Body Plethysmography; Work; angiogenesis; base; blood perfusion; capillary; cigarette smoking; cohort; density; design; drug discovery; human disease; in vivo; inhibitor/antagonist; insight; molecular modeling; normal aging; programs; repaired; response; theories

DESCRIPTION (provided by applicant): Non-invasive, regional assessment of lung function has the potential to markedly enhance early diagnosis and management of disease, to accelerate drug discovery and trials, and to provide fundamental insights into the root causes of disease. In this proposal, we aim to address a fundamental question of emphysema pathogenesis thorough a systematic study of lung function and structure using techniques developed over the first funding cycle. These techniques include measurements of pulmonary ventilation and perfusion, alveolar oxygen tension, and a sensitive measure of lung microstructure using hyperpolarized magnetic tracers, as well as several well-established methods in pulmonary medicine. The proposed research is designed specifically to corroborate or refute a molecular model of emphysema progression that is currently under widespread debate. Despite extensive investigation, it is still not clear which of the numerous and varied presentations of emphysema corresponds to the fundamental cause of the disease, or even if one principal cause can be identified. Nonetheless, a large body of current research suggests that altered expression of one or more mediators of angiogenesis may be the first step in the disease. This alteration degrades the capillary endothelium's ability to repair itself, resulting in cell death, reduced perfusion, and ultimately tissue destruction. Although in vivo imaging methods cannot replace the powerful molecular techniques in use today, they can provide a more complete picture of the action of disease or therapy on the body. In this study, we first demonstrate a comprehensive, self-consistent, and validated set of pulmonary measurements and evaluate sensitivity to disease. We then apply these measurements to three animal models of emphysema in order to evaluate time ordering and spatial correlation of the various aspects of pulmonary dysfunction. By comparing these measurements to testable predictions of the disease model, we hope to elucidate the first stages of this devastating disease.

描述（由申请人提供）：肺功能的非侵入性区域评估有可能显著增强疾病的早期诊断和管理，加速药物发现和试验，并提供对疾病根本原因的基本见解。在这项提案中，我们的目标是解决一个基本的问题，肺气肿的发病机制，通过系统的研究肺功能和结构使用的技术开发的第一个资金周期。这些技术包括测量肺通气和灌注，肺泡氧张力，和一个敏感的测量肺微观结构使用超极化磁示踪剂，以及几个完善的方法在肺部医学。这项拟议的研究是专门设计来证实或反驳目前正在广泛辩论的肺气肿进展的分子模型。尽管进行了广泛的研究，但仍然不清楚肺气肿的众多和不同的表现中哪一种对应于疾病的根本原因，或者即使可以确定一个主要原因。尽管如此，目前的大量研究表明，一种或多种血管生成介质的表达改变可能是疾病的第一步。这种改变降低了毛细血管内皮的自我修复能力，导致细胞死亡，灌注减少，最终组织破坏。虽然体内成像方法不能取代当今使用的强大的分子技术，但它们可以提供疾病或治疗对身体作用的更完整的图像。在这项研究中，我们首先展示了一个全面的，自我一致的，并验证了一套肺测量和评估疾病的敏感性。然后，我们将这些测量结果应用于三种肺气肿动物模型，以评估肺功能障碍各个方面的时间顺序和空间相关性。通过将这些测量结果与疾病模型的可测试预测进行比较，我们希望阐明这种毁灭性疾病的第一阶段。