A Compact, Cardiopulmonary Support Device

描述(申请人提供)：这项第一阶段资助的目标是开发和测试一种紧凑型心肺支持装置(CCSD)。这种设备可以泵送、输送气体和加热血液。CCSD通过静脉静脉(VV)或静脉动脉(VA)插管连接到患者身上，并提供呼吸支持，如体外膜氧合(ECMO)和类似于脑室辅助装置的搏动性心脏支持。与ECMO电路不同，所有这些功能都在一个紧凑、低阻的器件中完成。因此，CCSD具有少量的血液接触表面积和低切变的血流。这导致对红细胞、血小板和白细胞的低损伤和低激活，允许在没有输血产品的情况下进行数月的呼吸支持，并且比ECMO的并发症发生率更低。该设备旨在为患有严重急性呼吸衰竭或慢性肺部疾病的患者提供呼吸支持，如果需要，还可提供心脏支持。慢性肺部疾病的唯一长期治疗方法是肺移植，但在过去十年中，等待治疗的人数增加了300%。在这种情况下，CCSD将i)在等待名单上的患者之间架起桥梁，直到找到合适的捐赠器官，ii)支持移植后有呼吸窘迫的患者，以及iii)可能允许使用边缘捐赠器官进行移植。在美国，每年有超过15万人受到急性呼吸衰竭的影响，死亡率为34%-65%。对于这些患者，该设备将允许更少的侵入性机械通气，减少呼吸机导致的器官衰竭，帮助康复，并降低死亡率。密歇根大学已经进行了重要的初步设计工作，以达到具有高气体交换、低血流阻力和高度生物兼容性的CCSD设计。第一阶段将用于制造该设计，并确保其满足以下可行性规格：CCSD具有最小的停滞区域，CCSD在体外和体内可以泵送和充分充氧高达5 L/分钟的血液，并且CCSD可以在体外运行一周而不发生泄漏。为了测试这些规格，将追求以下特定目标：特定目标1：使用计算流体力学优化设备血液流场特定目标2：制造用于性能测试的CCSD原型特定目标3：使用甘油进行体外测试，以检查CCSD的泵送能力。特定目标#4：进行体外血液测试以确定CCSD气体交换功能和瘀区特定目标#5：对CCSD进行体外、7天的耐受性测试特定目标#6：对CCSD进行短期(8小时)体内测试，以证明其安全性和有效性。具体目标2和5将在MC3，Inc.进行。具体目标1、3、4和6将在密歇根大学进行。公共卫生相关性这笔赠款将导致开发一种新型紧凑型心肺支持装置(CCSD)，它可以提供呼吸和心脏支持。新的CCSD将改善严重急性呼吸衰竭或慢性肺部疾病患者的治疗选择。

DESCRIPTION (provided by applicant): The objective of this Phase I grant is to develop and test a compact cardiopulmonary support device (CCSD). This device pumps, transfers gas, and warms blood. The CCSD is attached to the patient via venovenous (VV) or venoarterial (VA) cannulation and supplies respiratory support like extra-corporeal membrane oxygenation (ECMO) and pulsatile cardiac support similar to a ventricular assist device. Unlike ECMO circuits, all these functions are accomplished within one compact, low-resistance device. Therefore, the CCSD has a small amount of blood contact surface area and a low-shear blood flow. This leads to low damage and activation to red blood cells, platelets, and leukocytes, allowing for respiratory support for months without infused blood products and a lower complication rate than ECMO. The device is intended to provide respiratory and, if needed, cardiac support for patients with severe acute respiratory failure or chronic pulmonary disease. The only long-term treatment for chronic pulmonary disease is lung transplantation, but the waiting list has increased 300% over the last decade. In this situation, the CCSD would i) bridge patients on the waiting list until a suitable donor organ could be found, ii) support patients with respiratory distress after transplantation, and iii) might allow for transplantation with marginal donor organs. Acute respiratory failure affects more than 150,000 people per year in the US, with mortality rates of 34-65%. For these patients, the device would allow for less aggressive mechanical ventilation, reducing ventilator induced organ failure, aiding recovery, and reducing mortality. Significant preliminary design work has been performed at the University of Michigan to arrive at a CCSD design with high gas exchange, low blood flow resistance, and a high degree of biocompatibility. Phase I will be used to fabricate that design and ensure that it meets the following feasibility specifications: the CCSD has minimal areas of stasis, the CCSD can pump and fully oxygenate up to 5 L/min of blood both in vitro and in vivo, and the CCSD can operate in vitro for one week without leaking. To test these specifications, the following specific aims will be pursued: Specific Aim #1: Optimize device blood flow fields using computational fluid dynamics Specific Aim #2: Fabricate CCSD prototypes for performance testing Specific Aim #3: Perform in vitro testing using glycerol to examine pumping ability of the CCSD. Specific Aim #4: Perform in vitro blood tests to determine CCSD gas exchange function and stasis regions Specific Aim #5: Perform in vitro, seven-day durability testing of the CCSD Specific Aim #6: Perform short-term (< 8 hr) in vivo testing of the CCSD to prove safety and efficacy. Specific Aims 2 and 5 will be performed at MC3, Inc. Specific Aims 1, 3, 4 and 6 will be performed at the University of Michigan. PUBLIC HEALTH RELEVANCE This grant will result in the development of a novel compact cardiopulmonary support device (CCSD) that can supply both respiratory and cardiac support. The new CCSD will improve treatment options for patients with either severe acute respiratory failure or chronic pulmonary disease.