Paracorporeal Artificial Lung Development

描述（来自申请人摘要的逐字）： 单肺和双肺移植的成功和热情， 捐献的肺已经逐渐供不上了目前，平均等待时间为2 等待名单死亡率为30%。一个原型Paracket 人工肺（PAL）由MC 3（安阿伯，MI）设计和制造，用于高 气体交换效率和非常低的血流阻力。最初的PAL是 由我们的合作者（UTMB）植入肺动脉-肺动脉 （PA-PA）配置，并支持正常绵羊（N=8）的气体交换， 到7天。通过人工肺的总PA流量的平均压差 为8 mm Hg（3个Wood单位）; 8只绵羊中有4只在球囊完全充盈后存活 (full但8只绵羊中有4只不能耐受右心衰竭。 并发症包括由于断裂（2个样本端口， 2-套管断开）。因此，必须对原型PAL进行修改， 包括：1）低阻力气体交换器，其具有2）流入柔量 3）夹头螺母套管连接，无血样端口。的 本研究计划近期目标是： 具体目标1。根据我们的 初步经验，纳入以下设计变更1）降低 具有2）流入顺应室和3）夹头螺母的阻力气体交换器 无血样端口的套管连接。 具体目标2。a）在健康绵羊中进行7天研究，以确定 PAL气体交换性能和血流动力学增强的最大水平 可实现的。B）我们将利用我们最近开发的，临床相关的 急性呼吸窘迫综合征（ARDS）动物模型（n=8） 在急性呼吸窘迫期间初步评价PAL性能 急性呼吸窘迫综合征（ARDS）7天。 对于第二阶段，我们将进行一项前瞻性、随机结局研究 比较标准化压力控制机械通气与PAL， 我们的LD 50和LD 100 ARDS模型，以确定长期生存或桥接 严重呼吸衰竭时的能力。该项目将完成 PAL开发和产出未来的患者管理和选择方案 PAL人体安全试验。 拟定商业应用： PAL的商业潜力是直接的，并具有显着的潜力 附带技术。 直接的市场将作为肺移植的桥梁。 长 长期的潜力是作为一种替代移植的终末期肺病（一个更大的 人口）。 本文的研究成果无疑也将对日常生活的设计有所裨益 心肺转流（CPB）氧合器（仅在美国每年就有30万例， 市价9000万元）。

DESCRIPTION (Verbatim from the Applicant's Abstract): Despite the widespread success and enthusiasm f single and double lung transplantation, demand for donor lungs has steadily outgrown supply. Currently, the average wait is two years, with 30 percent wait-list mortality. A prototype Paracorporeal Artificial Lung (PAL) was designed and built by MC3 (Ann Arbor, MI) for high gas exchange efficiency and very low blood flow resistance. The initial PAL was implanted by our collaborators (UTMB) in a pulmonary artery-to-pulmonary artery (PA-PA) configuration, and supported gas exchange in normal sheep (N=8) for up to 7 days. Mean pressure gradient at total PA flow across the artificial lung was 8 mm Hg (3 Wood units); 4 of 8 sheep survived complete balloon inflation (full flow) but 4 of 8 sheep were intolerant from right heart failure. Complications included exsanguination (4/8) due to breakage (2 sample ports, 2-cannula disconnection). Therefore, necessary prototype PAL modifications include: 1) a lower resistance gas exchanger with 2) an inflow compliance chamber, and 3) collet-nut cannula connections without blood sample ports. The immediate goal of this research plan is to: Specific Aim 1. Build a working prototype for the modified PAL, based on our initial experience, to incorporate the following design changes 1) lower resistance gas exchanger with 2) inflow compliance chamber and 3) collet-nut cannula connections without blood sample ports. Specific Aim 2. a) Perform 7-day studies in healthy sheep to determine the maximum level of PAL gas exchange performance and hemodynamic augmentation achievable. b) We will utilize our recently developed, clinically relevant (LD50) model of acute respiratory distress syndrome (ARDS) in adult sheep (n=8) to initially evaluate PAL performance during acute respiratory distress syndrome (ARDS) for seven days. For Phase II, we will perform a prospective, randomized outcomes study comparing standardized pressure controlled mechanical ventilation versus PAL in our LD50 and LD100 models of ARDS to determine long-term survival or bridge capability during severe respiratory failure. This project will complete the PAL development and yield patient management and selection protocols for future PAL human safety trials. PROPOSED COMMERCIAL APPLICATION: The commercial potential for the PAL is both immediate and has the potential for significant spin-off technology. The immediate market will be as a bridge to lung transplant. The long term potential is as an alternative to transplant for end-stage lung disease (a much larger population). The research proposed will also undoubtedly benefit the design of routine cardiopulmonary bypass (CPB) oxygenators (300,000 cases a year in the U.S. alone at a market price of $90,000,000).