Perfusion Device for Lung Evaluation and Transplantation

描述（由申请人提供）：2400万美国人患有终末期肺病，这是美国第四大死亡原因，目前有2,122名候选人在肺移植等待名单上。肺气肿和慢性阻塞性肺病是导致肺移植的最常见诊断。合适的肺供体的有限可用性已成为移植界日益关注的问题。这项SBIR提案的主要影响将是增加被认为可接受移植的肺的数量，并减少移植名单上的患者等待时间。这将是专注于开发肺低温灌注保存装置和方法的技术的结果，该装置和方法将使肺离体保存长达24小时。此外，该设备应允许评估器官质量;它也将成为肺部研究界可用的重要研究工具。该I期SBIR提案的目的是通过在便携式低温肺灌注原型中12小时后对肺功能进行离体常温测试来确定低温机器灌注保存肺的可行性。便携式肺灌注原型将在实验过程中不断优化，以实现最佳性能。将通过低温（4-8 ℃）灌注保存12小时的猪肺与在冰上冷静态保存的肺进行比较。器官质量将在体外进行评估，其中肺将在37 ℃下灌注和通气，同时使用生化和生理工具来确定肺功能。在本可行性研究结束时，将对便携式临床前肺灌注原型设计进行审查，并进行失效模式和影响分析，以确保其安全性和易用性，从而允许其临床应用。如果在第一阶段证明可行性，拟议的第一阶段研究将进入第二阶段。将通过证明灌注保存后肺功能在统计学上优于当前实践静态储存对照来验证可行性。在II期研究中，将进行猪肺移植模型研究以及离体人肺评价。 公共卫生相关性：该提案旨在实现技术突破，有可能解决国家对可移植肺的关键需求。本提案中描述的器械有可能通过对目前不考虑移植的边缘器官和受控无心跳供体进行评估、修复和批准，将肺供体库增加到满足当前需求的水平。

DESCRIPTION (provided by applicant): Twenty four million Americans are affected with end-stage lung disease which is the 4th leading cause of death in the US, and there are currently 2,122 candidates on the lung transplant waiting list. Emphysema and chronic obstructive pulmonary disease are the most common diagnoses leading to lung transplantation. The limited availability of suitable lung donors has become an increasing concern in the transplant community. The primary impact of this SBIR proposal will be increased numbers of lungs being considered acceptable for transplantation and decreased patient waiting times on the transplant list. This will be a consequence of technology focused on development of a lung hypothermic perfusion preservation device and methods that will maintain lungs ex vivo for up to 24 hours. Furthermore, the device should permit evaluation of organ quality; and it will also result in an important research tool being available to the lung research community. The objective of this Phase I SBIR proposal is to determine the feasibility of hypothermic machine perfusion preservation of the lung by ex vivo normothermic testing of lung function after 12 hours in a portable hypothermic lung perfusion prototype. The portable lung perfusion prototype will be continuously optimized during the course of the experiments for optimal performance. Swine lungs preserved by hypothermic (4-8¿C) perfusion for 12 hours will be compared with lungs submitted to cold static preservation on ice. Organ quality will be assessed ex vivo where the lungs will be perfused and ventilated at 37¿C while biochemical and physiological tools are used to determine lung function. At the conclusion of this feasibility study the portable preclinical lung perfusion prototype design will be reviewed and subjected to failure mode and effects analysis to insure the safety and ease of use that will permit its clinical application. The proposed Phase I study will progress to Phase II if feasibility is demonstrated in Phase I. Feasibility will be verified by demonstration of statistically better lung function after perfusion preservation than current practice static storage controls. In Phase II porcine lung transplant model studies as well as ex vivo human lung evaluations will be performed. PUBLIC HEALTH RELEVANCE: This proposal aims at the technical breakthrough with the potential to address critical national needs for transplantable lungs. The device described in this proposal has the potential to increase the lung donor pool to levels that would satisfy current demand by evaluation, reconditioning and approval of marginal organs and controlled non-heart beating donors that are presently not considered for transplantation.