Original pre-clinical science
Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion

https://doi.org/10.1016/j.healun.2011.11.007Get rights and content

Background

The use of donation-after-circulatory-death (DCD) donors for lung transplantation has come into practice. In this study we investigated whether DCD lungs can be resuscitated after warm ischemia with normothermic ex vivo lung perfusion (EVLP).

Methods

Four hours after cardiac arrest, beagle dogs were divided into two groups (n = 6 each): those with static cold storage (SCS group) and those with normothermic EVLP (EVLP group), for 3.5 hours. Physiologic lung functions were evaluated during EVLP. In both groups, the left lungs were then transplanted and reperfused for 4 hours to evaluate post-transplant lung functions. Lung tissue adenosine triphosphate (ATP) levels were measured at given time-points.

Results

Lung oxygenation was significantly improved with EVLP (p < 0.01), and lung oxygenation at the end of EVLP significantly reflected post-transplant lung oxygenation (r = 0.99, p < 0.01). Post-transplant lung oxygenation was significantly better in the EVLP group than in the SCS group (p < 0.05). Both dynamic pulmonary compliance and wet-to-dry lung weight ratio 4 hours after transplantation were also significantly better in the EVLP group than in the SCS group (p < 0.05). Microthrombi in the donor lungs before transplantation were microscopically detected more often in the SCS group. The lung tissue ATP levels 4 hours after transplantation were significantly higher in the EVLP group compared with the SCS group (p = 0.03).

Conclusions

Normothermic ex vivo lung perfusion could resuscitate DCD lungs injured by warm ischemia, and may ameliorate ischemia–reperfusion injury.

Section snippets

Animals

Beagle dogs, weighing from 9 to 15 kg (Kitayama Labes Co., Hongo Farm, Yamaguchi, Japan), were used in this study. All animals received humane care in compliance with the “Principals of Laboratory Animal Care,” formulated by the U.S. National Society for Medical Research, and the Guide for the Care and Use of Laboratory Animals, prepared by the U.S. Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication 85–23, revised 1996). The study was

Physiologic lung functions

One dog from each group died from severe pulmonary edema 2.5 hours after transplantation. They were excluded from the data analysis at 3 hours and 4 hours after transplantation.

Lung oxygenation was significantly improved by EVLP (p < 0.01; Figure 1A). Specifically, PaO2 at baseline of EVLP and the end of EVLP were 437 ± 68 mm Hg and 558 ± 35 mm Hg, respectively. Both dynamic pulmonary compliance and pulmonary vascular resistance were stable during EVLP (Figure 1B and C).

Post-transplant lung

Discussion

In this study we have demonstrated that normothermic EVLP with db-cAMP and NTG could resuscitate DCD lungs injured by 4 hours of warm ischemia, and could ameliorate ischemia–reperfusion injury compared with static cold storage. Cypel and colleagues established a successful prolonged EVLP system using an acellular perfusate, and suggested that this system can be used to assess, maintain and treat injured donor lungs.14 We have adapted their technique and confirmed excellent lung performance

Disclosure statement

The authors have no conflicts of interest to disclose.

Part of this work was presented at the 31st annual meeting and scientific sessions of the International Society for Heart and Lung Transplantation, April 2011, San Diego, California.

References (26)

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    Indeed, any strategy that could increase the amount of acceptable WIT has the potential to increase the number of possible donors. In the laboratory, the use of EVLP alone or with targeted drug therapy has been reported previously as a means to assess and recondition lungs from DCD donors.12,13 In a study from the University of Virginia (Charlottesville, VA), Charles and colleagues12 showed that injured porcine lungs were rendered transplantable after reconditioning with EVLP and the use of an adenosine A2B receptor antagonist.

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    The same research group suggests that lung harvesting in non-controlled cardiac arrest situations may present some advantages in terms of lung function because of the absence of an agonic phase [67]. Several experimental studies have shown that EVLP normothermic preservation is probably better than prolonged cold ischaemia [32,68]. Other pig lung experimental studies have shown that re-cooling the lungs after EVLP it probably not necessary if transplantation surgery is performed a few minutes after EVLP [69].

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