Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial

Slama, Alexis; Schillab, L.; Barta, M.; Benedek, Aris; Mitterbauer, Andreas; Höetzenecker, Konrad; Taghavi, Shahrokh; Láng, György; Matilla, José Ramon; Ankersmit, Hendrik Jan; Hager, Helmut; Roth, Georg A.; Klepetko, Walter; Aigner, Clemens

doi:10.1016/j.healun.2017.02.011

Cited by 118 publications

(96 citation statements)

References 28 publications

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“…Consistently, the synthases involved in large-sized HA polymerization were found to be up-regulated in homogenates of perfused lungs, whereas the shorter-chain HA synthase was downregulated. These observations suggest that production of high-MW HA could represent a potential mechanism that underlies the beneficial influences of EVLP observed in lung transplantation (10)(11)(12). Indeed, high-MW HA was shown to exert various protective effects in different lung injury models (22) and after orthotopic lung transplantation (27).…”

Section: Discussionmentioning

confidence: 87%

“…This is clearly problematic as recognition of EVLP effects seems to be crucial not only for improving the procedure but also to properly evaluate treatment efficacy. A better comprehension of EVLP biologic influences would likewise contribute to the implementation of newly emerging applications in lungs that meet transplant acceptability criteria (12) and in injured lungs outside transplantation procedures (13).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, ex vivoperfused marginal lungs demonstrated a reduced incidence of primary graft dysfunction compared with untreated standard organs (10,11). Of interest, the transplantation outcome of ex vivo-perfused optimal lungs was also improved compared with lungs subjected to standard procurement (12). Finally, using an experimental model of acute respiratory distress syndrome, Mehaffey and colleagues (13) demonstrated that the lung perfusion procedure can be used to ameliorate sepsis-induced lung injury.…”

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confidence: 99%

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Influence of ex vivo perfusion on the biomolecular profile of rat lungs

et al. 2018

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Despite increasing clinical adoption, biologic influences of ex vivo lung perfusion (EVLP) remain insufficiently elucidated. The aim of the current study was to investigate biomolecular changes induced by EVLP in rat lungs. EVLP was maintained for 180 min. Hyaluronan, mediators, and cells were assessed in the perfusate. Gene expression, signaling pathways, and ATP content were investigated in lung tissue. EVLP induced the release of medium-high molecular weight hyaluronan and transcription of hyaluronan synthases ( P< 0.001). Increasing concentrations of inflammatory mediators were detected in the perfusate ( P < 0.001). Perfused lungs exhibited a distinctive transcriptional signature compared with organs examined before or after surgery/procurement ( P = 0.003). Up-regulated genes were involved in inflammation and its regulation, apoptosis/survival, heat shock, and oxidative stress response ( q = 0). Down-regulated genes were related to lymphocyte function ( q = 0). The NF-κB, signal transducer and activator of transcription 3, ERK1/2, p38, Akt, and stress-activated protein kinase/JNK signaling pathways were modulated by EVLP ( P < 0.05). Most of these biomolecular changes were examined and confirmed in additional experiments that were performed in lungs procured from donation after cardiocirculatory death after 180 min of warm ischemia. The current study demonstrates that EVLP broadly affects the lung biomolecular phenotype. These findings improve our comprehension of the effects exerted by the procedure and encourage additional research in preclinical models to implement therapeutic interventions.-Lonati, C., Bassani, G. A., Brambilla, D., Leonardi, P., Carlin, A., Faversani, A., Gatti, S., Valenza, F. Influence of ex vivo perfusion on the biomolecular profile of rat lungs.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Influence of ex vivo perfusion on the biomolecular profile of rat lungs

et al. 2018

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“…These findings suggest obvious advantages of IFLT over CLT as far as marginal donor organs are concerned.IRI can also contribute to later graft failure by triggering irreversible ischemic type biliary lesions (ITBL) or by promoting rejection via activation of innate immunity 2. Since the NMP technique is available for other organs, such as lung,16 heart, 17 and kidney, 18 the concept of IFOT is probably applicable in these organ transplant procedures as well. In conventional transplant procedures, the profound inflammatory response during IRI is one of the key triggers of allograft rejection 14,15.…”

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confidence: 99%

The first case of ischemia-free organ transplantation in humans: A proof of concept

Guo

Zhao

et al. 2018

American Journal of Transplantation

131

109

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Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.

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“…There are data confirming the safety of the use of lungs obtained from ‘extended criteria’ donors (ECD) or through donation after circulatory death (DCD), suggesting that the current standard criteria for lung donation are too restrictive . Strategies of donor management and allograft preservation to increase the number of transplantable donor lungs are being investigated . Ex vivo lung perfusion (EVLP) has become an important tool in the assessment, preservation, and reconditioning of DCD, ECD, and standard donor lungs …”

Section: Introductionmentioning

confidence: 99%

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion

Spratt

Mattison

Kerns

et al. 2020

Clinical Transplantation

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Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain‐dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood‐based EVLP.

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Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial

Cited by 118 publications

References 28 publications

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

The first case of ischemia-free organ transplantation in humans: A proof of concept

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion

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