Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion.

J Heart Lung Transplant. 2017 May 20. pii: S1053-2498(17)31802-8. doi: 10.1016/j.healun.2017.05.021. [Epub ahead of print] Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion. Ilker Iskender, MD, MSc,Tugba Cosgun, MD, Stephan Arni, PhD et al +Walter Weder, MD, MD Ilhan Inci

DOI: http://dx.doi.org/10.1016/j.healun.2017.05.021

Background

Ex vivo lung perfusion (EVLP) improved the process of donor-lung management. Cytokine accumulation during EVLP has been shown to correlate with a worse outcome after lung transplantation. Our objective was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model.

Methods

Pig donor lungs were preserved for 24 hours at 4°C, followed by 12 hours of EVLP according to the Toronto protocol. The perfusate was continuously run through an absorbent device (CytoSorb^®) via a veno-venous shunt from the reservoir in the filter group. EVLP was performed according to the standard protocol in the control group (n = 5 each). EVLP physiology, lung X-ray, perfusate biochemistry, inflammatory response, and microscopic injury were assessed.

Results

Cytokine filtration significantly improved airway pressure and dynamic compliance during the 12-hour perfusion period. Lung X-rays acquired at the end of perfusion showed increased consolidation in the control group. Electrolyte imbalance, determined by increased hydrogen, potassium, and calcium ion concentrations in the perfusate, was markedly worsened in the control group. Glucose consumption and lactate production were markedly reduced, along with the lactate/pyruvate ratio in the filter group. Cytokine expression profile, tissue myeloperoxidase activity, and microscopic lung injury were significantly reduced in the filter group.

Conclusions

Continuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and electrolyte imbalance through the suppression of anaerobic glycolysis and neutrophil activation in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function.