A Leukocyte Filter Does Not Provide Further Benefit During Ex Vivo Lung Perfusion

Abstract

Normothermic ex vivo lung perfusion (EVLP) allows for assessment and reconditioning of donor lungs. Although a leukocyte filter (LF) is routinely incorporated into the EVLP circuit; its efficacy remains to be determined. Twelve pig lungs were perfused and ventilated ex vivo in a normothermic state for 12 hours. Lungs (n = 3) were allocated to four groups according to perfusate composition and the presence or absence of a LF in the circuit (acellular ± LF, cellular ± LF). Acceptable physiologic lung parameters were achieved during EVLP; however, increased amounts of pro-inflammatory cytokines (TNF-α and IL-6) and leukocytes in the perfusate were observed despite the presence or absence of a LF. Analysis of cells washed off the LF demonstrates that it trapped leukocytes although being ineffective throughout perfusion as it became saturated over 12 hours of EVLP. We conclude that there is no objective evidence to support the routine incorporation of a LF during EVLP as it does not provide further benefit and its removal does not appear to cause harm. The lack of hypothesized benefit to a LF may be because of the saturation of the LF with donor leukocytes, leading to similar amounts of circulating leukocytes still present in the perfusate with and without a LF.

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

“…Leukocyte filters have been incorporated into lung perfusion systems to capture circulating leukocytes but have uncertain efficacy, likely due to saturation of the filter. 44 Nevertheless, NMP provides the unique opportunity to deliver directed therapies to the kidney, which may include targeting leukocytes. Delivery of other agents that specifically target endothelial cells, ameliorate IRI, and/or attempt to modulate endothelial cell major histocompatibility complex antigen expression using gene therapies have also been demonstrated by several groups.…”

Ex vivo lung perfusion as a human platform for preclinical small molecule testing

“…One investigation sought to decrease the amount of inflammatory cytokines present by placing an adsorbent membrane in line within the circuit to trap inflammatory cytokines (22). Our group recently used a leukocyte filter in a rat model to decrease cytokine levels and improve lung function (23), while another group claims such filters offer little benefit in a pig EVLP model (24). Another study delivered high-dose antibiotics to perfused lungs prior to their transplant, with resultant decreases in allograft bacterial burden observed (25).…”

Machine perfusion of thoracic organs

“…Debate continues about the best conditions for EVLP with regards to cellular versus acellular composition of the perfusate (138)(139)(140)(141), the importance of left atrial pressure (138,142), positive versus negative pressure ventilation (143), the use of leucocyte (144) or cytokine filters (145,146) in the circuit, the oxygenation level of the perfusate (147), and the role of hemofiltration (148). Research is ongoing to identify clinical biomarkers in the perfusate such as cytokines (149), endothelial markers (150), adhesion molecules (151), metabolomics (152) and to investigate imaging techniques (153,154) before and after EVLP that may be predictive of graft function after transplantation.…”