Development of Percutaneous DLC for Total Cavo-pulmonary Assistance

 描述(由申请人提供)：Fontan手术或全腔静脉肺动脉连接术(TCPC)是治疗复杂的单心室先天性心脏病患者的标准姑息手术。TCPC绕过心脏，将下腔静脉和上腔静脉(下腔静脉和上腔静脉)直接连接到右肺动脉。然后，单个脑室被保留，用于将含氧血液泵入体循环。Fontan手术使数千名患者受益，但Fontan循环在多年后失败，死亡率相对较高。 Fontan循环衰竭导致终末器官功能障碍，原因是中心静脉压升高导致静脉充血，以及低心输出量导致动脉血液灌注量降低。对于失败的Fontan患者来说，唯一有效的选择是心脏移植，但这些患者中的大多数都太过虚弱，无法成为移植候选者。需要腔肺辅助(CPA)通过Fontan连接从SVC/IVC泵入静脉血以逆转Fontan衰竭的病理生理。我们的最终目标是在TCPC和血泵之间建立一个方便和安全的连接，建立一个可移动的经皮CPA系统。我们的使能技术是世界上最复杂的双腔套管(DLC)之一。只需一次经皮静脉插管，这种DLC就可以轻松地将TCPC连接到商业血泵上，而无需进行大手术。这一CPA系统将把失败的Fontan患者连接到：1)心脏移植，2)康复，和/或3)进一步的心脏重建手术。在OU一期研究中，工作样机在我们的绵羊模型中显示出高达4.5%L/分钟的血流量，并完全逆转了Fontan循环衰竭(n=5)，实现了总CPA。在此第二阶段SBIR中，我们将根据第一阶段的结果优化设计，并制造最终的商用质量CPA DLC原型，用于台架测试和体内5天存活研究。具体目的1：设计和制作一种可用于非卧床CPA的经皮DLC。DLC上设计了两把薄膜伞，以防止输液流量再循环，确保高效可靠的性能。这些伞不会阻止从上腔静脉和下腔静脉流向肺动脉的血流，确保了在CPA系统发生故障时的安全性。两个输液口引导单独的血液流向每把伞，消除血液停滞和相关的血栓形成。粒子图像测速仪(PIV)验证的CFD将用于优化设计，以实现最高性能和最小的血栓形成可能性。具体目标2：在模拟环路台架测试中测试CPA DLC原型。台架测试将包括性能/可靠性评估、一个月的耐久性测试和PIV流程研究。具体目标3：在我们的TCPC绵羊模型上测试CPA DLC原型。短期活体研究(N=5)将测试CPA DLC的可行性、性能和可靠性。长期的5天体内研究(N=8)将测试性能、可靠性、耐用性和生物兼容性。虽然CPA DLC市场规模不大，但对需要CPA的患者的影响是重大的。

 DESCRIPTION (provided by applicant): The Fontan procedure or total cavopulmonary connection (TCPC) is a standard palliative surgery for patients with complex single ventricle congenital heart anomalies. TCPC connects the inferior and superior vena cava (IVC and SVC) directly to the right pulmonary artery, bypassing the heart. The single ventricle is then reserved for pumping oxygenated blood to the systemic circulation. The Fontan procedure has benefited thousands of patients, but the Fontan circulation fails years later with relatively high mortality. The failing Fontan circulation causes end organ dysfunction due to venous blood congestion from elevated central venous pressure and low arterial blood perfusion from low cardiac output. The only effective option for the failing Fontan patient is heart transplant, but most of these patients are too sick to be transplant candidates. Cavopulmonary assist (CPA) is needed to pump venous blood from SVC/IVC through the Fontan connection to reverse failing Fontan pathophysiology. Our ultimate goal is to create a convenient and secure connection between the TCPC and the blood pump, establishing an ambulatory percutaneous CPA system. Our enabling technology is one of the world's most complex double lumen cannula (DLC). Through only one percutaneous venous cannulation, this DLC can easily connect the TCPC to a commercial blood pump without major surgery. This CPA system will bridge the failing Fontan patient to: 1) heart transplant, 2) recovery, and/or 3) further reconstructive heart surgery. In ou phase I study, the working prototype demonstrated up to 4.5 l/min blood flow in our sheep model and completely reversed failing Fontan circulation (n=5), achieving total CPA. In this Phase II SBIR, we will optimize the design based on our Phase I results, and fabricate a final commercial quality CPA DLC prototype for bench test and 5 day survival in vivo studies. Specific Aim 1: To design and fabricate a percutaneous DLC for ambulatory CPA application. Two thin membrane umbrellas are designed on the DLC to prevent infusion flow recirculation, ensuring efficient and reliable performance. These umbrellas do not block the blood flow from SVC and IVC to pulmonary artery, guaranteeing safety if the CPA system malfunctions. Two infusion openings guide separate blood flow to each umbrella, eliminating blood stagnancy and associated thrombosis formation. Particle image velocimetry (PIV) validated CFD will be used to optimize the design for maximum performance and minimal thrombotic potential. Specific Aim 2: To test the CPA DLC prototype in a simulated mock loop bench test. Bench testing will include performance/reliability evaluation, one month durability test, and PIV flow study. Specific Aim 3: To test the CPA DLC prototype in our TCPC sheep model. Short term in vivo studies (N=5) will test CPA DLC feasibility, performance, and reliability. Long term 5 day in vivo studies (N=8) will test performance, reliability, durability, and biocompatibility. Although the CPA DLC market is small, the impact on the patients that need CPA is significant.