Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death

Beller JP1, Byler MR1, Money DT1, Chancellor WZ1, Zhang A1, Zhao Y1, Stoler MH2, Narahari AK1, Shannon A1, Mehaffey JH1, Tribble CG1, Laubach VE1, Kron IL3, Roeser ME4. ( Charlottesville, :            

J Heart Lung Transplant. 2020 Jan;39(1):74-82. doi: 10.1016/j.healun.2019.09.009. Epub 2019 Sep 18.                      

Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs.

A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion.

After transplant, left lung-specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm H2O vs. 10.2 ± 3.5 ml/cm H2O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1β expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group.

EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.

Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.  KEYWORDS:  DCD; ex vivo lung perfusion; lung preservation; lung transplant; transplantation                  PMID:  31761511    DOI:  10.1016/j.healun.2019.09.009