Normothermic Liquid Ventilation as a Method to Rehabilitate Lungs with Ischemia-Reperfusion Injury for Transplantation in an Ex-Vivo Rat Model

Abstract

Lung transplantation remains the only curative treatment for patients with end-stage pulmonary disease. Lung ischemia-reperfusion injury is a major contributor to post-transplant allograft dysfunction and a major cause of donor organ non-utilization. The alveolar macrophage is a key inflammatory mediator in lung ischemia-reperfusion injury. Ex-vivo lung perfusion has been investigated to rehabilitate lungs before transplant but has failed to provide significant improvements after ischemic insult. Here a novel method for ex-vivo lung reconditioning after significant ischemia-reperfusion injury with improved, clinically relevant physiologic parameters using liquid ventilation is described. These physiologic improvements are the result of the mechanical clearance of alveolar macrophages and inflammatory cytokines which blunt the release of additional inflammatory cytokines halting the propagation of ischemia reperfusion injury. While the wide applicability of these findings to large animal or human transplantation is yet to be explored, these findings represent a method for lung reconditioning from significant ischemic injury that could widen the lung organ donation pool and make a positive clinical impact on patient outcomes.