Compliant Thoracic Artificial Lungs

顺应性胸腔人工肺

• 批准号: 8011512
• 负责人: Keith E Cook
• 金额: $ 35.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8011512
• 关键词: Acute; Animal Model; Animals; Benchmarking; Blood Circulation; Blood flow; Carbon Dioxide; Cardiac Output; Chest; Chronic; Chronic lung disease; Coagulation Process; Data; Development; Device Designs; Devices; Disease model; Distal; Ensure; Exercise; Extracorporeal Membrane Oxygenation; Filtration; Functional disorder; Gases; Goals; Health; Heart; Housing; In Vitro; Inflammation; Left atrial structure; Liquid substance; Long-Term Effects; Lung; Lung Transplantation; Lung diseases; Mechanical ventilation; Mechanics; Metabolic; Methods; Modeling; Organ; Outcome; Output; Patients; Performance; Physiology; Pulmonary Artery Branch; Pulmonary Hypertension; Pulmonary Vascular Resistance; Pulmonary artery structure; Pulsatile Flow; Pump; Resistance; Right Ventricular Function; Right ventricular structure; Sheep; Simulate; Staging; Structure; System; Testing; Time; Transplant Recipients; Transplantation; Ventricular; Work; artificial lung; base; design; electric impedance; engineering design; hemodynamics; improved; in vitro testing; in vivo; meetings; prototype; research clinical testing; respiratory

DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to develop compliant, thoracic artificial lungs (cTALs) that can be used as a bridge to transplant for patients with end-stage respiratory disease. As a bridge to lung transplantation, a cTAL would allow for more patients to be transplanted and improve outcomes. Blood flow to the cTAL comes from the pulmonary artery (PA), driven by the right ventricle. Blood flow returns to the distal PA or branch of the PA (PA-PA attachment) or the left atrium (PA-LA attachment). These devices are designed to supply a patient's full gas transfer requirements with significantly less coagulation and inflammation than with extracorporeal membrane oxygenation (ECMO). Our group's previous work has led to devices that met these goals in large animals. However, this work also indicates that the fluid mechanical impedance of these devices can cause a significant reduction in cardiac output (CO) when attached in the PA- PA configuration. If not for this reduction in CO, PA-PA attachment would be the ideal means of attaching cTALs, as it allows the natural lung to maintain its normal filtration and metabolic functions. The cause of the reduction in CO is due, in large part, to excessive cTAL impedance. The studies in this proposal are aimed at designing a cTAL with very low impedance such that it can be used in any attachment configuration with little to no reduction in CO. This design should also allow for increases in CO with exercise. Five studies are proposed to meet this goal. (1) The relationship between pulmonary system impedance and CO will be determined using an intact heart, large animal model. The developed relationship will be used to set impedance benchmarks for the design of an improved cTAL that causes little to no reduction in CO during PA-PA attachment. (2) Fluid structure interaction (FSI) modeling will be used to design a cTAL that meets the impedance benchmarks. Preliminary FSI and in-vitro data indicates that cTAL impedance can be reduced to at least 33-50% of current thoracic artificial lungs. This should result in large improvements in CO during cTAL use. (3) The selected design will be tested in-vitro under pulsatile flow to confirm hemodynamic performance. (4) The cTAL will be tested in-vivo to determine short term (< 8 hrs) gas exchange and hemodynamic performance in the PA-PA and PA-LA configurations at normal and elevated CO. Lastly, (5) the cTAL will be tested in-vivo over 14 days to assess device performance and animal physiology. All animal studies will utilize a model of pulmonary hypertension during chronic lung disease. The resulting device will be ready for pre- clinical testing. PUBLIC HEALTH RELEVANCE: The goal of this project is to design and test compliant artificial lungs. These devices will give chronic lung disease patients more time to find a donor lung and improve their health before and after transplantation.

描述（由申请人提供）：该提案的长期目标是开发顺应性胸部人工肺（cTAL），可作为终末期呼吸系统疾病患者进行移植的桥梁。作为肺移植的桥梁，cTAL 将允许更多患者接受移植并改善结果。流向 cTAL 的血流来自肺动脉 (PA)，由右心室驱动。血流返回远端 PA 或 PA 分支（PA-PA 附着）或左心房（PA-LA 附着）。这些设备旨在满足患者的全部气体传输需求，并且与体外膜肺氧合 (ECMO) 相比，凝血和炎症明显减少。我们小组之前的工作已经开发出在大型动物身上实现这些目标的设备。然而，这项工作还表明，当这些设备连接在 PA-PA 配置中时，其流体机械阻抗可能会导致心输出量 (CO) 显着减少。如果不是为了减少二氧化碳，PA-PA 连接将是连接 cTAL 的理想方式，因为它允许自然肺保持其正常的过滤和代谢功能。 CO 减少的原因在很大程度上是由于 cTAL 阻抗过高。本提案中的研究旨在设计一种阻抗极低的 cTAL，使其可用于任何附件配置，几乎不减少 CO 量。该设计还应允许运动时 CO 量增加。为了实现这一目标，提出了五项研究。 (1) 肺系统阻抗和 CO 之间的关系将使用完整的心脏、大型动物模型来确定。所开发的关系将用于为改进的 cTAL 设计设定阻抗基准，该改进的 cTAL 在 PA-PA 连接过程中几乎不会减少 CO 。 (2) 流固耦合 (FSI) 建模将用于设计满足阻抗基准的 cTAL。初步 FSI 和体外数据表明，cTAL 阻抗可降低至当前胸部人工肺的至少 33-50%。这应该会导致 cTAL 使用期间 CO 的大幅改善。 (3) 所选设计将在脉动流下进行体外测试，以确认血液动力学性能。 (4) cTAL 将在体内进行测试，以确定在正常和升高的 CO 条件下 PA-PA 和 PA-LA 配置中的短期（< 8 小时）气体交换和血流动力学性能。最后，(5) cTAL 将被经过 14 天的体内测试，以评估设备性能和动物生理学。所有动物研究都将利用慢性肺病期间的肺动脉高压模型。由此产生的设备将准备好进行临床前测试。公共健康相关性：该项目的目标是设计和测试合规的人工肺。这些设备将使慢性肺病患者有更多时间寻找供体肺，并在移植前后改善他们的健康状况。