Ex Vivo Lung Perfusion: Current Achievements and Future Directions

Prasad, Nikhil K.; Pasrija, Chetan; Talaie, Tara; Krupnick, Alexander S.; Zhao, Yunge; Lau, Christine L.

doi:10.1097/tp.0000000000003483

Cited by 16 publications

(13 citation statements)

References 74 publications

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“…Many genes associated with proliferation of connective tissue were also upregulated by the 4 procedures suggesting cell regeneration and tissue repair processes (Figure 5C). In the inflammatory response function which is well known to be activated by EVLP procedures, 1 many genes encoding inflammatory cytokines were similarly upregulated in the 4 groups, such as IL17F, IL22, IL1B, CSF3, IL6, CCL3L1, CCL4, TNF in link with increased expression of REL and NFKB2 , that encode transcription factors activating many inflammatory genes 24 (Figure 5D). Notably, IPA could not attribute a z score to the inflammatory response prediction in the adult dialysis group, due to an unclear balance between the significantly modulated genes contributing to the function, impairing the z score calculation by the IPA algorithm.…”

Section: Resultsmentioning

confidence: 92%

“…Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and improve the function of marginal lungs before transplantation and thereby EVLP has increased the pool of donor lungs with outcome results comparable to those of cold-preserved standard lungs. 1 During the EVLP procedure, oxidative stress and inflammatory responses occur as the organ is reperfused after the anoxic steps of donor lung extraction and preservation, corresponding to an ischemia-reperfusion response. Indeed during EVLP, there is expression of reactive oxygen species (ROS), 2 Damage-associated molecular pattern (DAMPs) molecules including high-mobility group box 1 3 and heat-shock protein 70, 4 as well as synthesis and liberation of inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

et al. 2021

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Background. Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes. Methods. We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters. Results. Adult and pediatric dialysis stabilized the electrolytic and metabolic profiles while maintaining acid-base and gas exchanges. Pediatric dialysis increased the level of IL-10 and IL-6 in the perfusate. Despite leading to modification of the perfusate composition, the 4 EVLP conditions did not affect the gene expression profiles, which were associated in all cases with increased cell survival, cell proliferation, inflammatory response and cell movement, and with inhibition of bleeding. Conclusions. Management of EVLP perfusate by periodic replacement and continuous dialysis has no significant effect on the lung function nor on the gene expression profiles ex vivo. These results suggest that the accumulation of dialyzable cell products does not significantly alter the lung cell response during EVLP, a finding that may have impact on EVLP management in the clinic.

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Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

et al. 2021

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“…Perhaps the most significant advantage of EVLP relates to its use as a therapeutic platform for administration of localized, targeted lung-specific therapies ( 61 , 65 , 66 ). Even without modifications, EVLP is associated with alterations in the donor lung environment from diminished release of inflammatory mediators and augmentation of anti-inflammatory signaling pathways ( 67 – 70 ).…”

Section: Novel Preservation Methodsmentioning

confidence: 99%

Novel approaches for long-term lung transplant survival

Miller

Allan

et al. 2022

Front. Immunol.

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Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.

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“…In 2011 Toronto group published their results in the New England Journal of Medicine (NEJM) reporting a series of 20 cases of lung transplantation using EVLP evaluated lungs with comparable outcomes to that of standard donors [66,69,70,72]. By using an optimal lung protective strategy consisting of a low tidal volume ventilation and a low flow rate combined with a centrifuge pump permitted assessment and organ viability up to 12 hours, the Toronto group reported a near 70% increase in transplant volume without significant changes in the donor pool [72,73].…”

Section: Ex-vivo Lung Perfusion (Evlp)mentioning

confidence: 99%

A Breath of Fresh Air - Lung Transplantation Has Come of Age

Keshavamurthy¹,

Russell²

2023

OBM Transplant

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A boundless spectrum of chronic lung diseases is said to effect over 500 million persons globally. Lung transplantation is a well-established therapeutic option for patients suffering from end-stage lung diseases, however waitlist mortality and primary graft failure remain major determinants as post-transplantation 5-year survival is just above 50 percent. Recent innovations in lung transplantation have been aimed at increasing organ availability, improving allograft quality, function, and longevity. Ex-vivo Lung Perfusion (EVLP) is an exciting modality responsible for multiple paths of lung allograft reconditioning as well as significantly extending preservation times. Mechanical circulatory support (MCS), specifically extracorporeal membrane oxygenation (ECMO) has consistently gained popularity not only for its use as a bridge to transplantation, but also its intraoperative role. In tandem, EVLP and ECMO have shown promising results in increasing the number of lung transplantations performed, therefore decreasing waitlist mortality. Primary graft dysfunction (PGD) and chronic lung allograft rejection (CLAD) continue to be the most feared predictors of poor outcomes. In this review we will highlight the historical progression of lung transplantation, its encumbrance, and the most recent advancements in promising techniques for long-term allograft protection and patient survival.

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Ex Vivo Lung Perfusion: Current Achievements and Future Directions

Cited by 16 publications

References 74 publications

Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

Novel approaches for long-term lung transplant survival

A Breath of Fresh Air - Lung Transplantation Has Come of Age

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