Perfusion Device for Lung Evaluation and Transplantation

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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.