Development of a Total Artificial Lung

在过去的40年里，使用机械装置（“人造器官”）来代替急性或慢性器官衰竭的重要器官功能已经从理论发展到重症监护床边。其中30年来，我们对人造器官的研究得到了美国国立卫生研究院的支持，由此产生的设备和技术现在用于临床治疗肺、心脏、肾脏和肝脏衰竭。其中一种技术（体外生命支持，ECMO）可以代替肺功能数周，从而使致命的急性肺病恢复。但ECMO过于复杂和侵入性，不能作为肺移植的桥梁。桥接系统是必要的，因为大多数肺移植患者在等待名单上死亡，因为许多潜在的肺供体不被接受，因为在没有机械支持的情况下，临界肺功能可能在术后死亡。一个可植入的假肺可以发挥3-6个月的功能，就像心室辅助装置已经应用于心力衰竭和移植一样，可以解决这两个问题。我们已经将我们实验室的专业知识应用于开发一种准躯体/可植入的全人工肺；由右心室灌注并能完全支持呼吸。我们已经在绵羊体内植入7天，证明了原型设计的安全性和有效性。基于我们的初步研究证明了原理，我们建议设计和测试一个完整的人工肺，以进行初步临床试验。在这项提议中，我们进一步打算在医学研究人员和生物工程师之间建立新的合作伙伴关系，他们在流体动力学、气体输送、人工器官发育、体外支持和肺生理学方面具有特定的专业知识，以开发和改进TAL，使其能够成功植入全肺替代品。

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.