Development of an Implantable "Plug and Play" TransApical to Aorta VAD

描述（由申请人提供）：心脏切开术后休克（未能脱离旁路）仍然是一个高度病态的事件。大约60%的患者会停止使用短期（平均5天）左心室辅助装置（LVAD），但这些患者中只有一半能存活到出院。同样，心源性休克（CS）是一种严重的临床疾病，导致大多数急性心肌梗死（AMI）的早期死亡，其中30天死亡率为50%，总死亡率为80-90%。目前所有用于治疗开心术后休克的左心室辅助装置都使用主动脉回血移植（或插管）和一根通过心尖的大插管（外径16mm）。我们的目标是开发一种即插即插式（P&P）经尖至主动脉VAD泵，该泵简单且易于在几分钟内插入，流量高达10 L/min，后负荷为100 mmHg，可提供长达3个月的可靠性能。通过立即减少左心室（LV）壁的压力和扩张，并防止LV扩大，我们的P&P经根尖至主动脉VAD泵将作为移植或从心源性休克中恢复的桥梁。我们的具体目标是：1)制造一个原型设计，包括高效，无血栓肝素生理盐水清洗滚针轴承，减少轴承摩擦，增加耐用性，提高泵效率，并防止血栓形成。其他修改包括扩大和缩短血路，以减少阻力和增加脉搏，并增加一个形成的金属盘，以方便手术附着。2)在不同转速下进行性能和耐久性台架测试。我们预计泵流量为10 L/min @ 17,500 RPM，后负荷为100 mmHg，泵控制器精度为5%。3个月的模拟环耐久性测试将评估故障或磨损。3)对我们的新原型P&P经根尖至主动脉VAD进行大型动物研究：在健康绵羊（n=10）中进行为期一天的研究，将确定P&P经根尖至主动脉VAD所能达到的左室辅助量，并将证明泵与室内结构（如二尖瓣前小叶和瓣下结构）的相互作用。这个性能测试将指导任何进一步的原型修改。利用最终的P&P经根尖至主动脉VAD原型设计以及新设计的便携式泵控制系统，我们将在健康绵羊（n=3）身上测试系统设计作为慢性动态装置的可行性，为期5天。第一阶段的成功完成将允许进一步完善第二阶段的长期动物试验，从而在大型动物损伤模型中进行临床前试验。灾难性心力衰竭是心脏手术后和一些心脏病发作后患者死亡的主要原因。我们已经设计、开发并将建造一个“即插即用”泵（圆珠笔大小），它可以在几分钟内直接插入衰竭的心脏，为血液循环提供全面支持。这种独特的设计将允许即时心脏支持长达3个月，以允许心脏恢复或作为移植的桥梁。我们的简单，易于插入泵将彻底改变机械心脏辅助领域。

DESCRIPTION (provided by applicant): Postcardiotomy shock (failure to wean from bypass) remains a highly morbid event. Roughly 60% of patients will wean from a short-term (mean 5 days) left ventricular assist device (LVAD), but only half of these patients will survive to discharge. Likewise, Cardiogenic Shock (CS) is a serious clinical condition responsible for a majority of early deaths from acute myocardial infarction (AMI) with 50% 30-day and 80-90% overall mortality. All current LVADs used to treat post-cardiotomy shock use a blood return graft (or cannula) to the aorta and a large cannula (>16 mm outer diameter) through the cardiac apex. Our goal is to develop a Plug and Play (P&P) TransApical to Aorta VAD pump that is simple and easily inserted within a few minutes with flows up to 10 L/min against 100 mmHg afterload for up to 3 months reliable performance. By immediately reducing left ventricle (LV) wall stress and distension and by preventing LV enlargement our P&P TransApical to Aorta VAD pump will serve as either a bridge to transplant or recovery from cardiogenic shock. Our specific aims are to: 1) Fabricate a prototype design that includes efficient, thrombus free heparin saline purged needle roller bearings, which decreases bearing friction, increases durability, improves pump efficiency, and prevents thrombosis generation. Other modifications include blood path enlargement and shortening to decrease resistance and increase pulsatility, and the addition of a formed metal disk to facilitate surgical attachment. 2) Perform bench testing for performance and durability at different RPM's. We anticipate a pump flow of 10 L/min @ 17,500 RPM against a 100 mmHg afterload with a pump controller accuracy of 5%. A mock loop durability test for 3 months will assess failure or wear. 3) Perform large animal studies of our new prototype P&P TransApical to Aorta VAD: One-day studies in healthy sheep (n=10) will determine the amount of LV assistance achievable by a P&P TransApical to Aorta VAD and will demonstrate the interaction of the pump with intraventricular structures such as the anterior leaflet of the mitral valve and sub valvular structures. This performance testing will direct any further prototype modifications. Utilizing the final P&P TransApical to Aorta VAD prototype design coupled with the newly designed portable pump control system, we will then test the feasibility of the system design as a chronic ambulatory device in healthy sheep (n=3) for 5 days. Successful completion of Phase I will allow further refinement for long-term animal testing in Phase II, leading to pre-clinical testing in a large animal injury model. Catastrophic heart failure is a leading cause of death in patients following heart surgery and in some patients following a heart attack. We have designed, developed and will build a working "plug and play" pump (the size of a ballpoint pen) that is inserted directly into the failing heart within minutes to provide total support of the circulation. This unique design will allow immediate heart support for up to 3 months to allow the heart to recover or serve as a bridge to transplantation. Our simple, easily inserted pump will revolutionize the field of mechanical heart assist.