Ex vivo lung perfusion for donor lung assessment and repair: a review of translational interspecies models

2020 ◽  
Vol 319 (6) ◽  
pp. L932-L940
Author(s):  
Aizhou Wang ◽  
Aadil Ali ◽  
Shaf Keshavjee ◽  
Mingyao Liu ◽  
Marcelo Cypel
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Small Animal ◽  
Lung Perfusion ◽  
Contributing Factors ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Advantages And Disadvantages ◽  
Number Of Patients ◽  
End Stage

For patients with end-stage lung disease, lung transplantation is a lifesaving therapy. Currently however, the number of patients who require a transplant exceeds the number of donor lungs available. One of the contributing factors to this is the conservative mindset of physicians who are concerned about transplanting marginal lungs due to the potential risk of primary graft dysfunction. Ex vivo lung perfusion (EVLP) technology has allowed for the expansion of donor pool of organs by enabling assessment and reconditioning of these marginal grafts before transplant. Ongoing efforts to optimize the therapeutic potential of EVLP are underway. Researchers have adopted the use of different large and small animal models to generate translational preclinical data. This includes the use of rejected human lungs, pig lungs, and rat lungs. In this review, we summarize some of the key current literature studies relevant to each of the major EVLP model platforms and identify the advantages and disadvantages of each platform. The review aims to guide investigators in choosing an appropriate species model to suit their specific goals of study, and ultimately aid in translation of therapy to meet the growing needs of the patient population.

Ex Vivo Lung Perfusion: A Review of Research and Clinical Practices

2020 ◽  
Vol 24 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Patrick G. Chan ◽  
Akshay Kumar ◽  
Kathirvel Subramaniam ◽  
Pablo G. Sanchez
Keyword(s):  
Lung Disease ◽  
Ex Vivo ◽  
Conventional Technique ◽  
Lung Perfusion ◽  
Clinical Practices ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Number Of Patients ◽  
End Stage ◽  
Potential Tool

End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.

scholarly journals Evaluation of the efficacy of a novel perfusion solution for normothermic ex vivo lung perfusion compared with Steen solution™ (animal experimental study)

2021 ◽  
Vol 23 (3) ◽  
pp. 82-89
Author(s):  
S. V. Gautier ◽  
O. M. Tsirulnikova ◽  
I. V. Pashkov ◽  
N. V. Grudinin ◽  
D. O. Oleshkevich ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Infectious Complications ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion ◽  
Perfusion Solution ◽  
Number Of Patients ◽  
Donor Lung ◽  
End Stage

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.

scholarly journals Ex vivo lung perfusion: how we do it

2021 ◽  
Author(s):  
John Santosh Murala ◽  
William Michael Whited ◽  
Amit Banga ◽  
Robert Castillo ◽  
Matthias Peltz ◽  
...  
Keyword(s):  
Operative Technique ◽  
Lung Transplant ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Fda Approval ◽  
End Stage ◽  
Waitlist Mortality ◽  
Established Treatment

AbstractLung transplantation is an established treatment for patients with end-stage lung disease. However, a shortage of donors, low lung utilization among potential donors, and waitlist mortality continue to be challenges. In the last decade, ex vivo lung perfusion (EVLP) has expanded the donor pool by allowing prolonged evaluation of marginal donor lungs and allowing reparative therapies for lungs, which are otherwise considered not transplantable. In this review, we describe in detail our experience with EVLP including our workflow, setup, operative technique, and protocols. Our multidisciplinary EVLP program functions with the collaboration of surgeons, pulmonologists, and EVLP nurses who run the pump. EVLP program has been a valuable addition to our program. Since Food and Drug Administration (FDA) approval in 2019, we experienced incremental increased lung transplant volume of 12% annually.

scholarly journals Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Max T. Buchko ◽  
Nasim Boroumand ◽  
Jeffrey C. Cheng ◽  
Alim Hirji ◽  
Kieran Halloran ◽  
...  
Keyword(s):  
Negative Pressure ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Ex Situ ◽  
Positive Pressure ◽  
Ex Vivo Lung Perfusion ◽  
Extended Criteria Donor ◽  
Negative Pressure Ventilation ◽  
Discharge From Hospital ◽  
End Stage

AbstractLung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.

One-year experience with ex vivo lung perfusion: Preliminary results from a single center

2018 ◽  
Vol 41 (8) ◽  
pp. 460-466 ◽  
Author(s):  
Achim Koch ◽  
Nikolaus Pizanis ◽  
Carolin Olbertz ◽  
Omar Abou-Issa ◽  
Christian Taube ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Lung Perfusion ◽  
Smoking History ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Extended Criteria Donor ◽  
Ventilation Time ◽  
Postoperative Ventilation ◽  
Lung Transplants ◽  
One Year

Objective: To enlarge the donor pool for lung transplantation, an increasing number of extended criteria donor lungs are used. However, in more than 50% of multi-organ donors the lungs are not used. Ex vivo lung perfusion offers a unique possibility to evaluate and eventually recondition the injured donor lungs. The aim of our study was to assess the enlargement of the donor pool and the outcome with extended criteria donor lungs after ex vivo lung perfusion. Patients and Methods: Data were prospectively collected in our lung transplant database. We compared the results of lung transplants after ex vivo lung perfusion with those after conventional cold static preservation. In total, 11 extended criteria donor lungs processed with ex vivo lung perfusion and 41 cold static preservation lungs transplanted consecutively between May 2016 and May 2017 were evaluated. Normothermic ex vivo lung perfusion was performed according to the Toronto protocol for 4 h. Cold static preservation lungs were stored in low-potassium dextran solution. Results: Ex vivo lung perfusion lungs before procurement had significantly lower PaO2/FiO2 (P/F) ratios and more X-ray abnormalities. There were no statistically significant differences for pre-donation ventilation time, smoking history, or sex. After reconditioning with ex vivo lung perfusion, 9 out of 11 processed lungs were considered suitable and successfully transplanted. The mean postoperative ventilation time and in-hospital stay were not significantly different in ex vivo lung perfusion and cold static preservation recipients. Conclusion: Ex vivo lung perfusion can safely be used in the evaluation of lungs initially considered not suitable for transplantation. The primary outcome was not negatively affected and normothermic ex vivo lung perfusion is a useful tool to increase the usage of potentially transplantable lungs.

Ex vivo lung perfusion made easy

2021 ◽  
Keyword(s):  
Molecular Weight ◽  
Lung Transplant ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Low Molecular Weight ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Transplant Center ◽  
Indispensable Tool

Ex vivo lung perfusion is an indispensable tool in the armamentarium of any lung transplant center. It helps to increase an already shrinking donor pool by offering a chance to assess suboptimal donor lungs in a systematic manner and improve them by treating them with low-molecular-weight perfusate. We offer a stepwise guide to carry out ex vivo lung perfusion on the donor lungs and criteria to accept them for transplants.

In lung transplantation, are pulmonary grafts from donors deceased from hanging as suitable as grafts from donors deceased from other causes?

2019 ◽  
Vol 30 (1) ◽  
pp. 30-32
Author(s):  
João Santos Silva ◽  
Anne Olland ◽  
Gilbert Massard ◽  
Pierre-Emmanuel Falcoz
Keyword(s):  
Lung Transplantation ◽  
Observational Studies ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Graft Dysfunction ◽  
Post Transplantation ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Study Type

Abstract A best evidence topic was constructed according to a structured protocol. The question addressed was whether pulmonary grafts from donors deceased from hanging offer the same benefit as grafts from donors deceased from other causes in lung transplantation. Of the 17 papers found, 4 provided the best evidence to answer the question. The authors, date, journal, country of publication, study type, group studied, relevant outcomes and results of these papers are tabulated. One study reported a large cohort of donors and analysed the outcomes by cause of death, reporting no differences in survival. The remaining 3 papers analysed observational studies on the outcomes of lung transplantation using pulmonary grafts from donors deceased from hanging, compared with donors deceased from other causes. No differences in the rates of post-transplantation pulmonary graft dysfunction and long-term overall survival were reported. Although the cohort of donors deceased from hanging is small, we conclude that these donors are an important contribution to the donor pool. Ex vivo lung perfusion may have a role in assessing graft viability in this scenario.

scholarly journals Ex Vivo Lung Perfusion: A Platform for Donor Lung Assessment, Treatment and Recovery

2021 ◽  
Vol 2 (4) ◽  
pp. 387-395
Author(s):  
Luke Milross ◽  
Chelsea Griffiths ◽  
Andrew J. Fisher
Keyword(s):  
Ex Vivo ◽  
Objective Assessment ◽  
Lung Perfusion ◽  
Limited Information ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Ex Vivo Lung Perfusion ◽  
Donor Lung ◽  
Lung Injuries ◽  
End Stage

Lung transplantation offers a lifesaving therapy for patients with end-stage lung disease but its availability is presently limited by low organ utilization rates with donor lungs frequently excluded due to unsuitability at assessment. When transplantation does occur, recipients are then vulnerable to primary graft dysfunction (PGD), multitudinous short-term complications, and chronic lung allograft dysfunction. The decision whether to use donor lungs is made rapidly and subjectively with limited information and means many lungs that might have been suitable are lost to the transplant pathway. Compared to static cold storage (SCS), ex vivo lung perfusion (EVLP) offers clinicians unrivalled opportunity for rigorous objective assessment of donor lungs in conditions replicating normal physiology, thus allowing for better informed decision-making in suitability assessments. EVLP additionally offers a platform for the delivery of intravascular or intrabronchial therapies to metabolically active tissue aiming to treat existing lung injuries. In the future, EVLP may be employed to provide a pre-transplant environment optimized to prevent negative outcomes such as primary graft dysfunction (PGD) or rejection post-transplant.

scholarly journals Developments in lung transplantation over the past decade

2020 ◽  
Vol 29 (157) ◽  
pp. 190132 ◽  
Author(s):  
Sophie C. van der Mark ◽  
Rogier A.S. Hoek ◽  
Merel E. Hellemons
Keyword(s):  
Lung Transplantation ◽  
Ex Vivo ◽  
Smoking Status ◽  
Lung Perfusion ◽  
Long Term Outcomes ◽  
Donor Pool ◽  
The Past ◽  
End Stage

With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.

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