Ambulatory Arteriovenous Carbon Dioxide Removal

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）影响美国1500 - 1700万人，是美国第四大死亡原因。当COPD达到终末期时，高碳酸血症而不是缺氧通常限制COPD患者的行走能力。肺减容手术仍在研究中。肺移植每年只有900例，因为等待供体的平均时间是两年，等待名单上的死亡率为30%。人工肺还需要几年的时间。我们开发了动静脉二氧化碳清除（AVCO 2 R），在简单的经皮动静脉分流中使用低阻力气体交换器，以实现几乎完全体外清除CO2的产生，仅需800-1200 mI/min的血流量。根据我们的动物和患者安全性试验，AVCO 2 R可减少每分钟通气量，同时PaO 2/FiO 2增加，WBC、血小板或补体无显著变化，同时维持CO2和pH稳态。目前，AVCO 2 R设计用于仰卧位患者的经皮穿刺，以治疗ARDS。 由MC 3（安阿伯，密歇根州）设计并制造了原型移动式AVCO 2 R（A-AVCO 2 R）气体交换器，用于高气体交换效率和非常低的血流阻力。最初的A-AVCO 2 R设计由德克萨斯大学医学分支（UTMB）成功植入，在正常绵羊体内提供了24小时的近完全CO2清除。在这一点上，必要的原型A-AVCO 2 R修改包括：1）优化用于移动动静脉CO2清除（A-AVCO 2 R）的氧合器设计，以及2）实施便携式吹扫气体控制系统。第一阶段研究计划的近期目标是解决A-AVCO 2 R设计中的主要问题，将这些变化制作成工作原型，然后在可走动的大型动物中长期（1周）测试该设计。对于II期，我们计划在绵羊CO2潴留模型中进行一系列长期（1个月）研究，为临床试验做准备，以实现我们的目标，即A-AVCO 2 R作为长期生存的管理技术或作为肺移植的桥梁。

DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) affects 15-17 million people in the United States and is the fourth leading cause of death in the U.S. When COPD reaches end-stage, hypercarbia, not hypoxia, usually limits the COPD patients' ability to ambulate. Lung Volume Reduction Surgery remains investigational. Lung transplantation is available to only 900/year as the average wait for a donor is two years with 30 percent wait-list mortality. An artificial lung is years away. We developed Arteriovenous Carbon Dioxide Removal (AVCO2R) with a low-resistance gas exchanger in a simple percutaneous arteriovenous shunt to achieve near-total extracorporeal removal of CO2 production with only 800-1200 mI/min blood flow. From our animal and patient safety trials, AVCO2R decreases minute ventilation with an increase in PaO2/FiO2 and no significant change in WBC, platelets, or complement while maintaining CO2 and pH homeostasis. Currently, AVCO2R is designed for percutaneous access in a supine patient as treatment for ARDS. A prototype Ambulatory AVCO2R (A-AVCO2R ) gas exchanger was designed and built by MC3 (Ann Arbor, Ml) for high gas exchange efficiency and very low blood flow resistance. The initial A-AVCO2R design was successfully implanted by the University of Texas Medical Branch (UTMB) to provide near total CO2 removal in a normal sheep for 24 hours. At this point, necessary prototype A-AVCO2R modifications include: 1) optimization of the oxygenator design for ambulatory arteriovenous CO2 removal (A-AVCO2R), and 2) implementation of a portable sweep gas control system. The immediate goal of this phase I research plan is to address the major problems in A-AVCO2R design, fabricate the changes into a working prototype, and then test the design chronically (1 week) in ambulatory large animals. For Phase II, we plan a series of long-term (1 month) studies in sheep models of CO2 retention to prepare for clinical trials to achieve our goal of A-AVCO2R as a management technique for long-term survival or as a bridge to lung transplantation.