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Transplant Suitability of Rejected Human Donor Lungs With Prolonged Cold Ischemia Time in Low-Flow Acellular and High-Flow Cellular Ex Vivo Lung Perfusion Systems

Okamoto, Toshihiro MD, PhD1,2,3; Wheeler, David RRT-NPS4; Farver, Carol F. MD5; McCurry, Kenneth R. MD1,2

doi: 10.1097/TP.0000000000002667
Original Basic Science—General

Background. Ex vivo lung perfusion (EVLP) has the potential to increase the number of donor lungs available for lung transplantation (LTx). While the current maximum cold ischemia time (CIT) for donor lungs in clinical LTx is around 8 hours, there are no data regarding the potential use of rejected donor lungs with CIT >8 hours before EVLP. The purpose of this study was to investigate the transplant suitability of lungs with a prolonged CIT in 2 EVLP systems.

Methods. Following prolonged CIT of 13.8 hours (range 9.0–19.5 h), 16 rejected human donor lungs were randomly divided and perfused using either low-flow acellular or high-flow cellular EVLP systems (n = 8, each). Transplant suitability was evaluated according to the standard criteria of each EVLP system.

Results. The high-flow cellular group was associated with a significantly lower transplant suitability (0% versus 37%, P = 0.027), significantly lower wet-to-dry ratio change (−0.71 ± 0.62 versus 0.43 ± 1.01, P = 0.035), and lower pathological score (1.62 ± 0.61 versus 3.00 ± 0.61, P = 0.163) than the low-flow acellular group. In both systems, inflammatory cytokines on perfusate (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, and IL-10) increased in a time-dependent manner and were significantly higher than those of controls with CIT <8 hours (P < 0.05).

Conclusions. The potential for reconditioning lungs with a CIT >8 hours is diminished compared with that for lungs having a shorter CIT due to severe ischemia reperfusion injury.

1 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.

2 Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH.

3 Transplant Center, Cleveland Clinic, Cleveland, OH.

4 Department of Cardiothoracic Anesthesia, Cleveland Clinic, Cleveland, OH.

5 Anatomic Pathology, Cleveland Clinic, Cleveland, OH.

Received 11 August 2017. Revision received 27 December 2018.

Accepted 16 January 2019.

The authors declare no conflicts of interest.

This research was supported by the donation of Rosy and Ray Park.

T.O. and D.W. participated in research design, performed the study, analyzed the data, and wrote the manuscript. C.F.F. and K.R.M. designed the study, interpreted all data, and wrote the manuscript.

Correspondence: Toshihiro Okamato, MD, PhD, 9500 Euclid Ave, Cleveland, OH 44195. (

Correspondence: Kenneth R. McCurry, MD, 9500 Euclid Ave, Cleveland, OH 44195. (

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