α 1 -Anti-trypsin improves function of porcine donor lungs during ex-vivo lung perfusion

Lin, Hongyuan; Chen, Manyin; Tian, Feng; Tikkanen, Jussi; Ding, Lei; Cheung, Hei Yu Andrew; Nakajima, Daisuke; Wang, Zhe; Mariscal, A.; Hwang, David; Cypel, Marcelo; Keshavjee, Shaf; Liu, Mingyao

doi:10.1016/j.healun.2017.09.019

Cited by 66 publications

(49 citation statements)

References 44 publications

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“…Although none were used in this study, there is interest in using EVLP as a platform to deliver adjunctive therapies aimed at ameliorating inflammation and other processes injurious to donor lungs . The use of prolonged EVLP with ADWB perfusate would likely provide a stable environment in which such therapies could be given sufficient time to have maximum effect.…”

Section: Discussionmentioning

confidence: 99%

“…Although none were used in this study, there is interest in using EVLP as a platform to deliver adjunctive therapies aimed at ameliorating inflammation and other processes injurious to donor lungs. [29][30][31][32][33][34][35][36][37][38] The use of prolonged EVLP with ADWB perfusate would likely provide a stable environment in which such therapies could be given sufficient time to have maximum effect. The use of ADWB does risk prolonging donor pro-inflammatory cytokines accompanying brain death or DCD, but this may be mitigated by the use of an in-line cytokine filter.…”

Section: Future Directionsmentioning

confidence: 99%

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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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“…Although none were used in this study, there is interest in using EVLP as a platform to deliver adjunctive therapies aimed at ameliorating inflammation and other processes injurious to donor lungs . The use of prolonged EVLP with ADWB perfusate would likely provide a stable environment in which such therapies could be given sufficient time to have maximum effect.…”

Section: Discussionmentioning

confidence: 99%

“…Although none were used in this study, there is interest in using EVLP as a platform to deliver adjunctive therapies aimed at ameliorating inflammation and other processes injurious to donor lungs. [29][30][31][32][33][34][35][36][37][38] The use of prolonged EVLP with ADWB perfusate would likely provide a stable environment in which such therapies could be given sufficient time to have maximum effect. The use of ADWB does risk prolonging donor pro-inflammatory cytokines accompanying brain death or DCD, but this may be mitigated by the use of an in-line cytokine filter.…”

Section: Future Directionsmentioning

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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“…The mechanisms of IRI are well documented and several interventions have tried to limit the extent of overall graft damage during the recovery phase . These include, but are not limited to, sphingosine‐1‐phosphate, alpha‐1‐anti‐trpysin, noble gases, and mesenchymal stem cells . However, assuming the graft has not suffered an irremediable insult, the organ ultimately reaches a stable plateau in lung function.…”

Section: Discussionmentioning

confidence: 99%

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Buchko

Stewart

Hatami

et al. 2019

American Journal of Transplantation

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Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n = 5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins, and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated. Perfusate lactate, lipid and branch chain amino acid (BCAA) concentrations were also analyzed to elucidate how substrates were being utilized over time. Lungs in the TPN group exhibited significantly better oxygenation. Perfusate sodium was more stable in the TPN group. In the control group, free fatty acids (FFA) were quickly depleted, reaching negligible levels early in the perfusion. Alternatively, BCAA in the control group rose continually over the perfusion demonstrating a shift toward proteolysis for energy substrate. In the TPN group, both FFA and BCAA concentrations remained stable at in vivo levels after initial stabilization. TNF‐α concentrations were lower in the TPN group. The addition of TPN in EVLP allows for better electrolyte composition, decreased inflammation, and improved graft performance.

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“…anti-bacterial, anti-viral, and anti-fungal agents to treat infection (122,123), anti-inflammatory molecules to block pro-inflammatory responses (124)(125)(126), cytoprotective and anti-ischemic metabolic agents (127)(128)(129), agents initiating or enhancing ischemic postconditioning, vasodilating agents to improve perfusion of the microvasculature, fibrinolytic agents to dissolve microthrombi (130), dehydration of tissue with perfusate with high oncotic pressure, etc. An advantage of this isolated MP setting is that these drugs could be given at higher doses than in vivo since there is no risk to harm other organs.…”

Section: Mp Of Thoracic Organs For Repair and Reconditioningmentioning

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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α 1 -Anti-trypsin improves function of porcine donor lungs during ex-vivo lung perfusion

Cited by 66 publications

References 44 publications

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

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

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Machine perfusion of thoracic organs

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