Reliability of Donor Lung Sampling in Lung Transplantation

Author(s):  
Bonnie T Chao ◽  
Andrew T Sage ◽  
Marcelo Cypel ◽  
Mingyao Liu ◽  
Jonathan Yeung ◽  
...  

Introduction: Ex vivo lung perfusion (EVLP) is a normothermic platform used to assess donor lungs. Many have studied biomarkers in lung injury, but it is unclear whether samples taken from one location are representative of the organ. Our objective was to investigate the uniformity of cytokine expression in tissue biopsies and in EVLP perfusates from various locations. Methods: In the tissue study, eight donor lungs were partitioned from apex to base. In each lung, three biopsies were taken from the third, sixth, and ninth slices, while two were taken from the lingula and an injury site. In the perfusate study, four samples were taken from four lobes in eight donors during EVLP. Expressions of IL-6, IL-8, IL-10, and IL-1β were measured using qPCR and ELISA. Results: In the tissue study, the mean intra-biopsy equal-variance F-value was 0.53. The median intra-biopsy coefficient of variation (CV) was 18%. In donors without gross focal injury, the mean comparisons of biopsies in each donor showed that the three consistent slices showed no differences and had a CV of 20%, which was similar to the intra-biopsy CV (p=0.80). Both the lingula and injury biopsies demonstrated larger differences from the rest. The median intra-lung CV of perfusates from different lobes was 4.9%. Conclusion: Intra-biopsy variances were consistent across biopsies. Lungs without gross focal injury demonstrated more consistent gene expression. The lingula is not a representative site due to high signal variability. The consistent measurements in EVLP perfusates provided a uniform picture of the inflammation.

2016 ◽  
Vol 42 (2) ◽  
pp. 95-98 ◽  
Author(s):  
Luis Gustavo Abdalla ◽  
Karina Andrighetti de Oliveira Braga ◽  
Natalia Aparecida Nepomuceno ◽  
Lucas Matos Fernandes ◽  
Marcos Naoyuki Samano ◽  
...  

Objective: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.


Author(s):  
S. V. Gautier ◽  
O. M. Tsirulnikova ◽  
I. V. Pashkov ◽  
N. V. Grudinin ◽  
D. O. Oleshkevich ◽  
...  

Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases. However, the number of transplant surgeries performed is not much. This is down to the high requirements on the condition of a potential lung donor and directly on the quality of the donor lung. This has significantly limited the number of optimal donors. Rehabilitation of donor lungs to optimal gas exchange indicators can be achieved and objectively assessed in the course of ex vivo lung perfusion (EVLP). The EVLP procedure is widespread in leading transplantation centers in Europe and North America. It allows to significantly expand the pool of donor lungs, thereby serving a greater number of patients in need of lung transplantation. The possibility of EVLP procedure using publicly available perfusion equipment was demonstrated. The optimized protocol fully demonstrated its reliability and efficiency. The developed perfusion solution had no statistically significant differences in comparison with the Steen SolutionTM, which in the future will serve as an alternative for EVLP procedure.


2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Triin Major ◽  
Alexandra L. Ball ◽  
John P. Stone ◽  
Rebecca J. Edge ◽  
Gloria Lopez-Castejon ◽  
...  

2016 ◽  
Vol 35 (4) ◽  
pp. S305
Author(s):  
J.R. Spratt ◽  
L.M. Mattison ◽  
P.A. Iaizzo ◽  
T. Iles ◽  
W.D. Payne ◽  
...  

2020 ◽  
Vol 55 (4) ◽  
pp. 1902222 ◽  
Author(s):  
Aaron Wong ◽  
Ricardo Zamel ◽  
Jonathan Yeung ◽  
Gary D. Bader ◽  
Claudia C. Dos Santos ◽  
...  

IntroductionThe ex vivo lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation.Materials and methodsRetrospective transcriptomics analyses were performed with peripheral tissue biopsies from “donation after brain death” lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP.Results22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models.ConclusionEVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.


2015 ◽  
Vol 34 (4) ◽  
pp. S39-S40 ◽  
Author(s):  
J.C. Yeung ◽  
R. Zamel ◽  
X. Bai ◽  
T.N. Machuca ◽  
M. Liu ◽  
...  

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