Ex vivo lung perfusion

Abstract

Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

“…Flow rate was also increased stepwise to reduce hemodynamic stress. Of note, in order to avoid hydrostatic edema, we elected to use a moderately low flow rate coupled with an open atrium strategy [13], though this approach is typically associated with high flow rates in the clinical setting [1]. Ventilation was started only when lung temperature reached the physiological range.…”

“…Though in EVLP rat models lungs are usually suspended from the tracheal and pulmonary cannulae [19, 21, 22, 26, 27, 29, 30], we elected to put the graft horizontally, similar to the clinical setting [1]. However, because rat lungs are fragile, we used an ad hoc modeled elastic surface to avoid excessive pressure to soft tissues.…”

“…The perfusion fluid used in this model has the same principal components of STEEN solution™ that is generally used in the clinical setting [1]. The fluid consisted of an extracellular-type solution supplemented with human serum albumin to reduce edema development, heparin to avoid clot formation, dextran to prevent leukocyte adhesion [31], and glucose as energy source.…”

“…However, graft shortage is a major limiting factor to clinical success. Indeed, it is estimated that only 15–20% of potential lungs from multiorgan donors are currently suitable for transplantation [1]. …”

The future direction and unmet needs of transplant immunosuppression

“…These findings were part of the rationale for a recently completed clinical trial of eculizumab, an antibody targeting C5 thereby inhibiting C5a formation, to mitigate DGF in kidney transplantation [15]. Finally, organ rehabilitation through the further development and expansion of ex vivo lung perfusion protocols will hopefully allow the future lung allografts to 'recover' and prevent IRI [16]. Ideally, therapeutic agents could be used in concert with ex vivo perfusion of lungs, livers, and kidneys to mitigate IRI.…”