Development of a Minimally Invasive Single Cannulation, Compact Single Port Pulsatile Ventricular Assist Device (sppVAD) for Total LV Support

开发用于全面左心室支持的微创单插管、紧凑型单端口脉动心室辅助装置 (sppVAD)

• 批准号: 10259308
• 负责人: Stephen R Topaz
• 金额: $ 22.5万
• 依托单位: W-Z BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259308
• 关键词: Alloys; Animals; Aorta; Apical; Biotechnology; Blood; Blood Circulation; Cannulas; Cannulations; Carbon Dioxide; Cardiac; Cardiac Output; Cardiogenic Shock; Clinical; Complex; Counterpulsation; Data; Development; Devices; Engineering; Excision; Extracorporeal Membrane Oxygenation; Goals; Heart; Heart Transplantation; Hour; Housing; Kentucky; Laboratory Animal Production and Facilities; Left; Left ventricular structure; Low Cardiac Output; Lung; Mechanics; Membrane; Memory; Multiple Organ Failure; Myocardial Infarction; Organ; Pathway interactions; Patients; Performance; Perfusion; Phase; Polyurethanes; Publications; Pump; Recovery; Research; Resistance; Respiratory Diaphragm; Safety; Scientist; Self-Help Devices; Small Business Innovation Research Grant; Stress; Stroke; Surgeon; System; Techniques; Technology; Testing; Thinness; Thoracic Surgical Procedures; Thoracotomy; Universities; Withdrawal; Work; artificial lung; ascending aorta; blood pump; design; experience; flexibility; hypoperfusion; implantation; improved outcome; in vitro testing; in vivo; innovation; invention; minimally invasive; mortality; multidisciplinary; myocardial injury; novel; prevent; prototype; research and development; sheep model; simulation; ventricular assist device

Cardiogenic shock (CS) is a serious condition of reduced cardiac output (CO) with a mortality as high as 40-50%. In severe CS, end organ hypoperfusion from low CO causes multi-organ failure and elevated left ventricle (LV) preload increases LV wall stress. For severe CS, venoarterial extracorporeal membrane oxygenation is most often used and is fastest way to reestablish circulation, but it fails to unload LV in > 50% of these patients. Percutaneous mechanical circulatory support (MCS) devices are used in severe CS but may not fully stabilize circulation. Non-percutaneous MCS devices supply total cardiac support but require open chest surgery for installation. Our goal is to develop a compact, single port, pulsatile ventricular assist device (sppVAD) for total LV support that employs a minimally invasive single cannulation technique for implantation. Compared to a continuous flow LVAD, our sppVAD system may further unload the LV when synchronized with the native heart for counterpulsation. Our enabling technologies that form the sppVAD system are a valved single lumen cannula (VSLC) and a valveless single port diaphragm displacement pump (spDDP). Our innovative sppVAD system features: 1) Minimally invasive trans-apical to aorta installation by one VSLC cannulation through small left thoracotomy; 2) Smaller spDDP without inlet/outlet valves and large dead space; 3) Lower blood resistance due to shorter pathway through LV via the VSLC that serves as both inlet and outlet cannula; 4) Dependable total LV unloading; 5) Potential LV internal/stroke work decrease with counterpulsation pumping. W-Z Biotech made an initial prototype of sppVAD system, which had 3.1 L/min pumping flow against 80 mm Hg afterload in mock loop testing. Our objective in this Phase I SBIR is to develop/fabricate new working prototype of sppVAD system (VSLC and spDDP) and to test sppVAD system prototype in mock loop and severe CS sheep model. Specific Aim 1: To develop/fabricate/bench test new working prototype of sppVAD system (VSLC and spDDP). The 22 Fr VSLC main body will be memory alloy wire reinforced polyurethane (PU). Two one-way inlet valves on VSLC wall will be in LV for blood withdrawal. Two one-way outlet valves on VSLC wall near tip and a one-way outlet valve on VSLC tip will be in ascending aorta for blood delivery. The spDDP will have rigid PU housing, a soft, flexible PU diaphragm membrane, and a 50 mL pump volume. Only one 3/8” blood port will be made on spDDP for direct connection to VSLC. This sppVAD system will be tested in a bench mock loop. Specific Aim 2: To test sppVAD system prototype in a severe CS sheep model. Our severe CS sheep model will be used to test our sppVAD system prototype for ease of insertion/deployment, LV unloading performance, counterpulsation capacity, and 6 hr reliability (n=5). The sppVAD system prototype design/fabrication/in vitro testing will be done at W-Z Biotech while the in vivo animal studies will be done at University of Kentucky. Upon project completion, the commercialized sppVAD system will provide total LV support to severe CS patients via only a minimally invasive single cannulation.

心源性休克(CS)是一种严重的心输出量(CO)减少的情况，死亡率高达 40%-50%。重度CS患者，低一氧化碳致终末器官低灌流可导致多器官衰竭和左侧抬高 心室(LV)预负荷增加了LV壁应力。对于重度CS，静脉-动脉体外膜 充氧是最常用的，也是重建循环最快的方法，但它无法将50%的人的左心室排出。 这些病人。经皮机械循环支持(MCS)装置可用于重症CS，但可能 还没有完全稳定循环。非经皮MCS设备提供完全心脏支持，但需要开放 用于安装的胸部手术。我们的目标是开发一种紧凑型、单端口、脉冲式心脏辅助装置 (SppVAD)用于全左室支持，采用微创单次插管技术进行植入。 与连续流LVAD相比，我们的sppVAD系统在与 用于反搏动的天然心脏。我们形成sppVAD系统的使能技术是有阀门的 单腔套管(VSLC)和无阀单端口隔膜活塞泵(SpDDP)。我们的 创新的sppVAD系统特点：1)一个VSLC经心尖至主动脉微创安装术 经左胸小切口插管：(2)较小的SPDDP，无进/出气门和大死腔； 3)由于通过同时作为入口和出口的VSLC通过LV的路径较短，因此血液阻力较低 插管；4)可靠的总LV卸载；5)潜在的LV内/每搏功随反搏而减少 抽水。W-Z生物技术公司制作了SPPVAD系统的初步样机，该系统的泵送流量为3.1L/min。 模拟回路试验中的80毫米汞柱后负荷。我们在第一阶段SBIR的目标是开发/制造新的 SppVAD系统的工作原型(VSLC和spDDP)，并在模拟回路中测试sppVAD系统的原型 和重症CS绵羊模型。具体目标1：开发/制造/台架测试新的工作样机 SppVAD系统(VSLC和spDDP)。22Fr VSLC主体将由记忆合金丝加固 聚氨酯(PU)。VSLC壁上的两个单向进气阀将在LV中用于抽血。两张单程票 VSLC尖端附近壁上的出口阀门和VSLC尖端上的单向出口阀门将位于升主动脉供血 送货。SPDDP将拥有坚硬的PU外壳、柔软、灵活的PU隔膜和一个50毫升的泵 音量。SpDDP上只有一个3/8“血口可直接连接到VSLC。该sppVAD系统 将在长椅模拟回路中进行测试。具体目标2：在严重的CS中测试sppVAD系统原型 绵羊模型。我们的Severe CS绵羊模型将用于测试我们的sppVAD系统原型，以便于 插入/展开、LV卸载性能、反搏能力和6小时可靠性(n=5)。这个 SppVAD系统的原型设计/制造/体外测试将在W-Z生物技术公司进行，而体内 动物研究将在肯塔基大学进行。项目完成后，商业化的sppVAD 该系统将仅通过一次微创单次插管为重症CS患者提供完全的LV支持。