Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism

Use of normothermic ex vivo lung perfusion (EVLP) was adopted in clinical practice to assess the quality of marginal donor lungs. Subnormothermic perfusion temperatures are in use among other solid organs to improve biochemical, clinical and immunological parameters. In a rat EVLP model of donation after circulatory death (DCD) lung donors, we tested the effect of four subnormothermic EVLP temperatures that could further improve organ preservation. Warm ischemic time was of 2 hours. EVLP time was of 4 hours. Lung physiological data were recorded and metabolic parameters were assessed. Lung oxygenation at 21°C and 24°C were significantly improved whereas pulmonary vascular resistance and edema formation at 21°C EVLP were significantly worsened when compared to 37°C EVLP. The perfusate concentrations of potassium ions and lactate exiting the lungs with 28°C EVLP were significantly lower whereas sodium and chlorine ions with 32°C EVLP were significantly higher when compared to 37°C EVLP. Also compared to 37°C EVLP, the pro-inflammatory chemokines MIP2, MIP-1α, GRO-α, the cytokine IL-6 were significantly lower with 21°C, 24°C and 28°C EVLP, the IL-18 was significantly lower but only with 21°C EVLP and IL-1β was significantly lower at 21°C and 24°C EVLP. Compared to the 37°C EVLP, the lung tissue ATP content after 21°C, 24°C and 28°C EVLP were significantly higher, the carbonylated protein content after 28°C EVLP was significantly lower and we measured significantly higher myeloperoxidase activities in lung tissues with 21°C, 24°C and 32°C. The 28°C EVLP demonstrated acceptable physiological variables, significantly higher lung tissue ATP content and decreased tissue carbonylated proteins with reduced release of pro-inflammatory cytokines. In conclusion, the 28°C EVLP is a non inferior setting in comparison to the clinically approved 37°C EVLP and significantly improve biochemical, clinical and immunological parameters and may reduce I/R injuries of DCD lung donors.

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Porcine Model of Donation after Cardiac Death (DCD) and Evaluation of Pulmonary Function Using Ex-vivo Lung Perfusion (EVLP)

University of Ottawa Journal of Medicine ◽

10.18192/uojm.v9i1.4180 ◽

2019 ◽

Vol 9 (1) ◽

pp. 40-48

Author(s):

Malek Dhane

Keyword(s):

Weight Gain ◽

Cardiac Death ◽

Porcine Model ◽

Ex Vivo ◽

Lung Perfusion ◽

Warm Ischemia ◽

The Body ◽

Cold Ischemia ◽

Ex Vivo Lung Perfusion ◽

Ischemic Time

Objective The limiting factor when using lungs from donors after cardiac death (DCD) is the duration of warm ischemic time, which is linked to reperfusion edema. Within the context of lung shortages, and in order to avoid transplanting damaged lungs, ex-vivo lung perfusion (EVLP) has emerged as an innovative tool to preserve and recondition donor lungs. Using the EVLP technique in a porcine model, the purpose of this study is to determine the duration of warm ischemia that donor lungs can tolerate before they are viewed as non-viable for transplant. Methods This study is comprised of 5 groups (n=2-6/group). Four groups endured different warm ischemic times, whilst the fifth group underwent cold ischemia. The lungs were subsequently perfused outside the body using the EVLP platform for four hours. Results 120 minutes of warm ischemia is more damaging for lungs than 120 minutes of cold ischemia, even after being reconditioned on the EVLP platform (50,4 ± 8,9% vs. 3,3 ± 3,4% of weight gain). This would signify that two hours of warm ischemia is incompatible with transplantation. However, 90 minutes and 60 minutes of warm ischemia seems to have less of an effect on pulmonary functions. Indeed, the lungs of both these groups had less than 14% of weight gain and maintained oxygenating capacities (PaO2/FiO2 of 514 ± 12 and 586 ± 0 mmHg respectively.) Conclusion Lungs having been submitted to less than 90 minutes of warm ischemia and evaluated with EVLP may be suitable candidates for transplantation.

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Feasibility of Lung Transplantation From Donation After Circulatory Death Donors Following Portable Ex Vivo Lung Perfusion: A Pilot Study

Transplantation Proceedings ◽

10.1016/j.transproceed.2017.04.010 ◽

2017 ◽

Vol 49 (8) ◽

pp. 1885-1892 ◽

Cited By ~ 9

Author(s):

J.G.Y. Luc ◽

K. Jackson ◽

J.G. Weinkauf ◽

D.H. Freed ◽

J. Nagendran

Keyword(s):

Pilot Study ◽

Lung Transplantation ◽

Ex Vivo ◽

Lung Perfusion ◽

Donation After Circulatory Death ◽

Ex Vivo Lung Perfusion ◽

Circulatory Death

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Lung Transplantation from Donation after Circulatory Death Donors Following Portable Ex-Vivo Lung Perfusion: Post-Hoc Analysis of OCS Lung EXPAND Trial

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2019.01.806 ◽

2019 ◽

Vol 38 (4) ◽

pp. S320

Author(s):

L.J. Ceulemans ◽

A. Neyrinck ◽

G. Loor ◽

G. Warnecke ◽

M. Villavicencio ◽

...

Keyword(s):

Lung Transplantation ◽

Ex Vivo ◽

Lung Perfusion ◽

Donation After Circulatory Death ◽

Ex Vivo Lung Perfusion ◽

Post Hoc Analysis ◽

Post Hoc ◽

Circulatory Death

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Effects of immediate versus delayed ex-vivo lung perfusion in a porcine cardiac arrest donation model

The International Journal of Artificial Organs ◽

10.1177/0391398819841618 ◽

2019 ◽

Vol 42 (7) ◽

pp. 362-369 ◽

Cited By ~ 1

Author(s):

Carolin Olbertz ◽

Nikolaus Pizanis ◽

Hagen Bäumker ◽

Simon Becker ◽

Clemens Aigner ◽

...

Keyword(s):

Ex Vivo ◽

Lung Perfusion ◽

Large Animal Model ◽

Large Animal ◽

Ex Vivo Lung Perfusion ◽

Promising Tool ◽

Group I ◽

Low Potassium ◽

Dextran Solution ◽

Circulatory Death

Objective:Ex-vivo lung perfusion is a promising tool to evaluate and recondition marginal donor lungs usually after a cold static preservation. The concept of continuous organ perfusion is supposed to reduce ischemic damage; however, the optimal perfusion protocol has not been established yet. The aim of this study was to compare immediate ex-vivo lung perfusion (I-EVLP) to delayed ex-vivo lung perfusion (D-EVLP) after a certain cold static preservation period on lung function in a large animal model.Methods:In a porcine model, lungs were procured after circulatory death and 60 min of no-touch warm ischemia. Lungs were preserved with single-flush cold low potassium dextran solution and prepared either for I-EVLP (n = 8) or stored cold for 9 h with subsequent D-EVLP (n = 8). Functional outcomes and morphology were compared during 4 h of ex-vivo lung perfusion, using STEEN SolutionTMas perfusion solution.Results:Pulmonary functional data, perfusate activities of lactate dehydrogenase, alkaline phosphatase, and products of lipid peroxidation did not differ significantly. There was a trend toward lower wet–dry ratio (I-EVLP: 13.4 ± 2.9; D-EVLP: 9.1 ± 2.5) and higher ΔpO2in D-EVLP group (I-EVLP: 209 ± 51.6 mmHg; D-EVLP: 236.3 ± 47.3 mmHg).Conclusion:In this donation-after-circulatory-death model, 9 h of cold static preservation followed by ex-vivo lung perfusion results in comparable pulmonary function to I-EVLP as indicated by oxygenation capacities and wet–dry ratio. Our findings indicate that prolonged cold static preservation prior to ex-vivo lung perfusion is as safe and effective as I-EVLP in the procurement of donor lungs.

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