Technique for Prolonged Normothermic Ex Vivo Lung Perfusion

Cypel, Marcelo; Yeung, Jonathan C.; Hirayama, S.; Rubacha, Matthew; Fischer, Stefan; Anraku, Masaki; Sato, Masaaki; Harwood, Steven; Pierre, Andrew; Waddell, Thomas K.; Perrot, Marc de; Liu, Mingyao; Keshavjee, Shaf

doi:10.1016/j.healun.2008.09.003

Cited by 452 publications

(453 citation statements)

References 31 publications

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“…The addition of adenosine receptor agonist/antagonist in the Steen solution augmented lung function while reducing proinflammatory cytokines, deleterious innate immunity pathways, and neutrophil vascular margination (43,44). Similar results have been shown in larger animals and human lungs using similar systems (45). Moreover, the delivery of IL-10 by EVLP adenoviral gene therapy to injured human donor lungs (46) resulted in improved lung function in pigs receiving therapy (47).…”

Section: Introductionsupporting

confidence: 53%

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Lama¹,

Belperio²,

Christie³

et al. 2017

JCI Insight

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Section: Introductionsupporting

confidence: 53%

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Lama¹,

Belperio²,

Christie³

et al. 2017

JCI Insight

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“…Detailed information about the technical aspects of the procedure can be found elsewhere. 10 NEVLP A model of donation after cardiac death (DCD) liver retrieval was created by inducing cardiac arrest by potassium chloride at the end of the vascular dissection during the organ retrieval procedure. Briefly, the donor pigs were sedated with ketamine (0.2 mg/kg), atropine (0.08 mg/kg), and midazolam (0.06 mg/kg), and induced with isoflurane (5%).…”

Section: Evlpmentioning

confidence: 99%

“…The details of both approaches to organ preservation before transplantation are described elsewhere. 10,11 SPME is a technology invented in the early 1990s. It already has an established position as a standard method in environmental and food analysis.…”

mentioning

confidence: 99%

Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery

Bojko

Goryński

Gómez‐Ríos

et al. 2014

Laboratory Investigation

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The techniques currently used for drug, metabolite, and biomarker determination are based on sample collection, and therefore they are not suitable for repeated analysis because of the high invasiveness. Here, we present a novel method of biochemical analysis directly in organ during operation without need of a separate sample collection step: solid-phase microextraction (SPME). The approach is based on flexible microprobe coated with biocompatible extraction phase that is inserted to the tissue with no damage or disturbance of the organ. The method was evaluated during lung and liver transplantations using normothermic ex vivo liver perfusion (NEVLP) and ex vivo lung perfusion (EVLP). The study demonstrated feasibility of the method to extract wide range of endogenous compounds and drugs. Statistical analysis allowed observing metabolic changes of lung during cold ischemic time, perfusion, and reperfusion. It was also demonstrated that the level of drugs and their metabolites can be monitored over time. Based on the methylprednisolone as a selected example, the impairment of enzymatic properties of liver was detected in the injured organs but not in healthy control. This finding was supported by changes in pathways of endogenous metabolites. The SPME probe was also used for analysis of perfusion fluid using stopcock connection. The evaluation of biochemical profile of perfusates demonstrated potential of the approach for monitoring organ function during ex vivo perfusion. The simplicity of the device makes it convenient to use by medical personnel. With the microprobe, different areas of the organ or various organs can be sampled simultaneously. The technology allows assessment of organ function by biochemical profiling, determination of potential biomarkers, and drug monitoring. The use of this method for preintervention analysis could enhance the decision-making process for the best possible personalized approach, whereas post-transplantation monitoring would be used for graft assessments and fast response in case of organ failure.

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“…Lung type I cells comprise approximately 95% of the alveolar surface and therefore form the major area of the lung, being critical for gas exchange (8). Type II cells are crucial for basic lung functions like surfactant production and tissue repair (9).…”

Section: Use Of Technetium-99m-labeled Eosinophils To Detect Active Ementioning

confidence: 99%

Use of Technetium-99m–labeled Eosinophils to Detect Active Eosinophilic Inflammation in Humans

Farahi

Loutsios

Peters

et al. 2013

Am J Respir Crit Care Med

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However, the additional flush after EVLP is expected to clear the medication from the vasculature. Furthermore, the accumulation of the drug in the extravascular space has been shown to be minimal and would have been rapidly dissipated once in vivo status had been reestablished (10). In our case there were no signs of fibrinolytic complication such as bleeding.With the success obtained in the Human Ex vivo Lung Perfusion trial and evidence from research studies demonstrating stable pulmonary function over prolonged normothermic perfusions over 12 hours, we believe that advanced lung preservation techniques should involve EVLP as a platform for accurate diagnosis and directed therapy (16). As opposed to our ongoing preclinical research using advanced molecular therapeutics such as adenoviral IL-10 gene therapy (17), in this case we used readily available clinical diagnostic techniques and a clinically proven, readily available medication to treat donor lungs in an almost guideline-based fashion, but in the ex vivo setting. Thus, this case exemplifies how the concept of personalized medicine for the donor organ can be applied in the field of lung transplantation.

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Technique for Prolonged Normothermic Ex Vivo Lung Perfusion

Cited by 452 publications

References 31 publications

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery

Use of Technetium-99m–labeled Eosinophils to Detect Active Eosinophilic Inflammation in Humans

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