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, : MR8BE@virginia.edu.)            

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

BACKGROUND:
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.

METHODS:
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.

RESULTS:
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.

CONCLUSIONS:
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