Development of a Total Artificial Lung

在过去的40年里，在急性或慢性器官衰竭中使用机械装置(人工器官)来替代重要器官功能已经从理论上进入了重症监护床边。在这些年中，我们对人工器官的研究得到了美国国立卫生研究院的支持，导致了现在临床上用于治疗肺、心脏、肾脏和肝脏衰竭的设备和技术。其中一种技术(体外生命支持，ECMO)可以替代肺功能数周，从而恢复原本致命的急性肺病。但ECMO太复杂、太有侵入性，不能作为肺移植的桥梁。需要一种桥接系统，因为大多数登记为肺移植的患者在等待名单上死亡，也因为许多潜在的肺捐赠者不被接受，因为在没有机械支持的情况下，临界肺功能可能在术后期间被证明是致命的。一个可以工作3-6个月的植入性人工肺可以解决这两个问题，就像脑室辅助装置应用于心力衰竭和移植一样。我们已经将我们实验室的专业知识应用到了体外/植入性全人工肺的开发中；该人工肺由右心室灌流，能够进行全呼吸支持。我们已经证明了原型设计的安全性和有效性，在绵羊身上植入了7天。根据我们的初步研究论证的原则，我们建议设计和测试一个完整的人工肺，以达到初步临床试验的目的。在这项提案中，我们还打算在医学研究人员和生物工程师之间建立新的合作和伙伴关系，他们在流体动力学、气体运输、人工器官开发、体外支持和肺生理学方面具有特定的专业知识，以开发和完善TAL，使其能够作为全肺替代成功地植入。

The use of mechanical devices ("artificial organs") to replace vital organ function in acute or chronic organ failure has gone from theory to the intensive care bedside in the last 40 years. For 30 of those years our research on artificial organs has been supported by NIH, resulting in devices and techniques now used clinically to treat lung, heart, kidney, and liver failure. One of these techniques (Extracorporeal Life Support, ECMO) can replace lung function for weeks resulting in recovery of otherwise fatal acute lung disease. But ECMO is too complex and invasive to serve as a bridge to lung transplantation. A bridging system is needed because most of the patients listed for lung transplantation die on the waiting list, and because many potential lung donors are not accepted because borderline lung function might prove fatal in the postoperative period without mechanical support. An implantable prosthetic lung which could function for 3-6 months would solve both of these problems, just as the ventricular assist device has been applied to cardiac failure and transplantation. We have applied the expertise of our laboratory to the development of a paracorporeal/implantable total artificial lung; perfused by the right ventricle and capable of total respiratory support. We have demonstrated safety and efficacy of a prototype design during seven days of implantation in sheep. Based on our preliminary studies demonstrating proof of principle, we propose to design and test a total artificial lung to the point of initial clinical trials. In this proposal, we further intend to establish a new collaboration and partnership between medical researchers and bioengineers who have specific expertise in fluid dynamics, gas transport, artificial organ development, extracorporeal support, and pulmonary physiology to develop and refine a TAL such that it can be implanted successfully as a total lung replacement.