Ilker Iskender1, Tugba Cosgun1, Stephan Arni1, Michael Trinkwitz2, Stefan Fehlings2, Yoshito Yamada1, Nikola Cesarovic3, Keke Yu4, Thomas Frauenfelder5, Wolfgang Jungraithmayr1, Walter Weder1, Ilhan Inci6. 1. Department of Thoracic Surgery, University Hospital Zurich-University of Zurich, Zurich, Switzerland. 2. Department of Cardiovascular Surgery, University Hospital Zurich-University of Zurich, Zurich, Switzerland. 3. Department of Surgical Research, University Hospital Zurich-University of Zurich, Zurich, Switzerland. 4. Department of Pathology, Shanghai Chest Hospital, Shanghai, People's Republic of China. 5. Department of Radiology, University Hospital Zurich-University of Zurich, Zurich, Switzerland. 6. Department of Thoracic Surgery, University Hospital Zurich-University of Zurich, Zurich, Switzerland. Electronic address: ilhan.inci@usz.ch.
Abstract
BACKGROUND: Ex vivo lung perfusion (EVLP) has improved the process of donor lung management. Cytokine accumulation during EVLP has been shown to correlate with worse outcome after lung transplantation. Our objective in this study 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.
BACKGROUND: Ex vivo lung perfusion (EVLP) has improved the process of donor lung management. Cytokine accumulation during EVLP has been shown to correlate with worse outcome after lung transplantation. Our objective in this study was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model. METHODS:Pigdonor 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.
Authors: Ahmed E Hozain; Yuliya Tipograf; Meghan R Pinezich; Katherine M Cunningham; Rachel Donocoff; Dawn Queen; Kenmond Fung; Charles C Marboe; Brandon A Guenthart; John D O'Neill; Gordana Vunjak-Novakovic; Matthew Bacchetta Journal: J Thorac Cardiovasc Surg Date: 2019-10-17 Impact factor: 6.439