Comparison of two strategies for ex vivo lung perfusion

Nilsson, Tobias; Gielis, Jan F.; Slama, Alexis; Hansson, Christoffer; Wallinder, Andreas; Ricksten, Sven‐Erik; Dellgren, Göran

doi:10.1016/j.healun.2017.07.001

Cited by 26 publications

(19 citation statements)

References 29 publications

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“…This model is different than previously described models because it utilizes a cellular perfusate and an open atrial technique. Previous publications showed similar results using cellular and acellular perfusates in humans 13,14 . We sought to validate the use of cellular perfusate with an open atrial system in a large animal model of sepsis induced lung injury.…”

Section: Discussionsupporting

confidence: 76%

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Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs

Nasir

Ménaouar²,

Landry³

et al. 2020

Preprint

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Background: The shortage of organ donors is a major challenge in lung transplantation. To expand the lung donor pool, ex-vivo lung perfusion (EVLP) has emerged as a platform for assessment and reconditioning marginal donor lungs. In this study a stable and reproducible large animal model of lipopolysaccharide (LPS) induced systemic inflammation and acute lung injury (ALI) was developed.Methods: Pigs (n=6) were anesthetized and monitored. After infusion of LPS (20 μg/kg) for 1 hour, followed by a 90-minute response period, lungs were procured and kept on ice for 2 hours, followed by 4 hours of EVLP. Pulmonary function, inflammatory biomarkers and edema formation were measured in vivo before procurement and during EVLP. Pro and anti-inflammatory cytokines were assayed in blood and in EVLP perfusate, which were collected before and every 30 minutes after LPS administration and EVLP.Results: LPS infusion resulted in significant hemodynamic instability, characterized by marked pulmonary hypertension, decreased systemic blood pressure and increased heart rate. This was associated with increased levels of TNFα, IL-10, IL-6, but no change in IL-1β. Ex vivo assessment of injured lungs showed graft dysfunction characterized by impaired gas exchange and edema formation. The inflammatory profile showed stable but elevated TNFα levels, and continuous production of interleukins during EVLP.Conclusion: We describe a reproducible large animal model of LPS-induced systemic inflammation and ALI. EVLP alone was unable to recondition severely injured lungs. These findings suggest that the EVLP platform requires adjuncts such as targeted anti-inflammatory agents to allow reconditioning of marginal donor lungs.

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Section: Discussionsupporting

confidence: 76%

“…Perhaps a cellular prime may further propagate the inflammatory response when compared to an acellular prime. However, previous studies did not show the superiority of acellular perfusate over cellular perfusate 13,14 . Furthermore, a porcine model of extended EVLP up to 24 hours showed an advantage of cellular over acellular perfusates 23 .…”

Section: Discussionmentioning

confidence: 81%

Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs

Nasir

Ménaouar²,

Landry³

et al. 2020

Preprint

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“…They differ in several aspects, mainly in the composition of perfusion solutions, EVLP circuit set-up, and perfusion flow (i.e. 40 or 70 ml/kg bw/min) and pressures [ 11 , 14 , 29 ]. The protocol of our study was developed to differ solely in the addition of erythrocytes to the perfusion solution in order to differentiate the impact of erythrocyte enrichment from other perfusion parameters in this prolonged setting of 12 h EVLP.…”

Section: Discussionmentioning

confidence: 99%

Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

et al. 2018

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BackgroundEx vivo lung perfusion (EVLP) is used by an increasing number of transplant centres. It is still controversial whether an acellular or cellular (erythrocyte enriched) perfusate is preferable. The aim of this paper was to evaluate whether acellular (aEVLP) or cellular EVLP (cEVLP) preserves functional lung ultrastructure better and to generate a hypothesis regarding possible underlying mechanisms.MethodsLungs of 20 pigs were assigned to 4 groups: control, ischaemia (24 h), aEVLP and cEVLP (both EVLP groups: 24 h ischaemia + 12 h EVLP). After experimental procedures, whole lungs were perfusion fixed, samples for light and electron microscopic stereology were taken, and ventilation, diffusion and perfusion related parameters were estimated.ResultsLung structure was well preserved in all groups. Lungs had less atelectasis and higher air content after EVLP. No significant group differences were found in alveolar septum composition or blood-air barrier thickness. Small amounts of intraalveolar oedema were detected in both EVLP groups but significantly more in aEVLP than in cEVLP.ConclusionsBoth EVLP protocols supported lungs well for up to 12 h and could largely prevent ischaemia ex vivo reperfusion associated lung injury. In both EVLP groups, oedema volume remained below the level of functional relevance. The group difference in oedema formation was possibly due to inferior septal perfusion in aEVLP.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0942-5) contains supplementary material, which is available to authorized users.

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“…Debate continues about the best conditions for EVLP with regards to cellular versus acellular composition of the perfusate (138)(139)(140)(141), the importance of left atrial pressure (138,142), positive versus negative pressure ventilation (143), the use of leucocyte (144) or cytokine filters (145,146) in the circuit, the oxygenation level of the perfusate (147), and the role of hemofiltration (148). Research is ongoing to identify clinical biomarkers in the perfusate such as cytokines (149), endothelial markers (150), adhesion molecules (151), metabolomics (152) and to investigate imaging techniques (153,154) before and after EVLP that may be predictive of graft function after transplantation.…”

Section: Lungmentioning

confidence: 99%

Machine perfusion of thoracic organs

Raemdonck¹,

Rega²,

Rex³

et al. 2018

J. Thorac. Dis.

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This article summarizes recent knowledge and clinical advances in machine perfusion (MP) of thoracic organs. MP of thoracic organs has gained much attention during the last decade. Clinical studies are investigating the role of MP to preserve, resuscitate, and assess heart and lungs prior to transplantation. Currently, MP of the cardiac allograft is essential in all type DCD heart transplantation while MP of the pulmonary allograft is mandatory in uncontrolled DCD lung transplantation. MP of thoracic organs also offers an exciting platform to further investigate downregulation of the innate and adaptive immunity prior to reperfusion of the allograft in recipients. MP provides a promising technology that allows pre-transplant preservation, resuscitation, assessment, repair, and conditioning of cardiac and pulmonary allografts outside the body in a near physiologic state prior to planned transplantation. Results of ongoing clinical trials are awaited to estimate the true clinical value of this new technology in advancing the field of heart and lung transplantation by increasing the total number and the quality of available organs and by further improving recipient early and long-term outcome.

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Comparison of two strategies for ex vivo lung perfusion

Abstract: Lung edema formation and decreased lung compliance occurs with both EVLP techniques but were more pronounced in the ACA group. Otherwise, there were no differences in lung function, inflammatory response, ischemia/reperfusion injury, or histopathologic changes between the EVLP techniques.

Cited by 26 publications

References 29 publications

Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs

Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs

Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

Machine perfusion of thoracic organs

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