The potential of ex vivo lung perfusion on improving organ quality and ameliorating ischemia reperfusion injury

Abstract

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx.

Keywords: ex vivo lung perfusion; graft function; ischemia reperfusion injury; lung transplantation.

Figure 1.. Ex Vivo Lung Perfusion ameliorates acute lung injury, dampens ischemia reperfusion injury and promotes tissue homeostasis

EVLP preservation has experimentally been shown to dampen (A) the release of the DAMP mt-DNA (B) and pro-inflammatory cytokines such as IL-1β and IL-18 while augmenting anti-inflammatory IL-10 levels. (C) EVLP compromises donor leucocyte migration associated with a decreased CCL2/3 and CCR1/2 expression thus inhibiting direct antigen presentation. (D) At the same time, EVLP reduces the infiltration of allogeneic T cells into the donor lung. (E) EVLP has been shown to promote the release of the tissue protective glycosaminoglycan, hyalouron contributing to the maintenance of lung tissue homeostasis. (F) EVLP preserves tissue integrity portrayed by functional zonula occludens in donor lungs.