Abstract
Ex vivo lung perfusion (EVLP) improved the algorithm in donor lung management. In the clinical EVLP setting, cytokine accumulation has been shown to correlate with worse outcome related to early graft dysfunction after lung transplantation. Our objective was to test the safety and efficacy of continuous cytokine filtration during prolonged EVLP in a pig model. Donor lungs were retrieved from randomly allocated female pigs and stored for 24h at 4°C. EVLP was performed during 12h according to the Toronto protocol. In the treatment group, the perfusate was continuously filtered with an absorbent device (CytoSorb®) via a veno-venous shunt after the reservoir, whereas we did not implement the additional filter in the control group (n=5/each). EVLP physiology, perfusate gases and biochemistry were monitored hourly, along with lung X-ray studies at the end of perfusion. Perfusate samples were analyzed with a multiplexed cytokine assay at 1h, 3h, 6h, and 12h time points. Cytokine filtration significantly improved dynamic compliance during the 12h perfusion period (Fig 1A). In the filter group, we characterized a decrease in both glucose consumption (Fig 1B) and lactate production, along with reduced amount of hydrogen, potassium, and calcium ions. Lung X-rays taken at the end of perfusion showed increased consolidation in the control group (Fig 1C). Interleukin (IL)-1α, IL-1β, IL-6, IL-8 (Fig 1D, shown as example), IL-10, IL-12, IL-18, and TNF-α levels were significantly reduced in the filter group. Continuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and suppressed anaerobic glycolysis in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function.
Published Version
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