Compliant Thoracic Artificial Lungs

顺应性胸腔人工肺

• 批准号: 7753676
• 负责人: Keith E Cook
• 金额: $ 36.94万
• 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/7753676
• 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; pre-clinical; prototype; public health relevance; 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）：本提案的长期目标是开发顺应性的胸部人工肺（ctal），可作为终末期呼吸系统疾病患者移植的桥梁。作为肺移植的桥梁，cTAL将允许更多的患者接受移植并改善预后。流向cTAL的血液来自肺动脉（PA），由右心室驱动。血流返回到远端动脉或动脉分支（PA-PA连接）或左心房（PA- la连接）。与体外膜氧合（ECMO）相比，这些设备旨在满足患者的全气体输送需求，显著减少凝血和炎症。我们小组之前的工作已经在大型动物身上实现了这些目标。然而，这项工作也表明，当连接在PA- PA配置时，这些装置的流体机械阻抗可以导致心输出量（CO）的显着降低。如果不是因为CO的减少，PA-PA附着将是附着cTALs的理想方式，因为它允许天然肺保持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阻抗过大。本提案中的研究旨在设计具有非常低阻抗的cTAL，以便它可以用于任何附件配置，而CO几乎没有减少。该设计还应允许CO随运动而增加。为实现这一目标，提出了五项研究。(1)采用完整心脏大动物模型确定肺系统阻抗与CO的关系。所开发的关系将用于为改进的cTAL设计设定阻抗基准，该cTAL在PA-PA连接期间几乎不会减少CO。(2)流体结构相互作用（FSI）建模将用于设计满足阻抗基准的cTAL。初步的FSI和体外数据表明，cTAL阻抗至少可以降低到目前胸部人工肺的33-50%。这将导致cTAL使用期间CO的大幅改善。(3)选择的设计将在体外脉动流下进行测试，以确认血流动力学性能。(4)将在体内测试cTAL，以确定在正常和升高的CO下PA-PA和PA-LA配置下的短期（< 8小时）气体交换和血流动力学性能。最后，(5)将在体内测试cTAL超过14天，以评估设备性能和动物生理学。所有的动物研究都将使用慢性肺病期间的肺动脉高压模型。由此产生的装置将准备进行临床前测试。公共卫生相关性：该项目的目标是设计和测试符合要求的人工肺。这些设备将使慢性肺病患者有更多的时间找到供体肺，并在移植前后改善他们的健康状况。