Original article
General thoracic
Cytokine Expression Profile in Human Lungs Undergoing Normothermic Ex-Vivo Lung Perfusion

Presented at the Poster Session of the Forty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2011.
https://doi.org/10.1016/j.athoracsur.2011.04.027Get rights and content

Background

A donor lung shortage prevents patients from receiving life-saving transplants. Ex-vivo lung perfusion (EVLP) is a viable means of expanding the donor pool by evaluating and potentially improving donor lung function. The metabolic and inflammatory effects of EVLP on human lung tissue are currently unknown. We sought to establish representative cytokine expression in human donor lungs meeting acceptable lung transplant criteria after prolonged normothermic EVLP.

Methods

Seven single human lungs not meeting traditional transplantation criteria for various reasons underwent normothermic EVLP. Lungs were perfused with deoxygenated colloid, rewarmed, and ventilated per standard protocol. Lung function was evaluated every hour. Biopsies were taken at 1, 6, and 12 hours. Inflammatory cytokines were quantitatively measured using a human cytokine magnetic bead-based multiplex assay.

Results

All lungs met traditional transplant criteria after EVLP. The partial pressure of arterial oxygen and physiologic lung function significantly improved (p < 0.05). No pulmonary edema was formed, and histology demonstrated no evidence of acute lung injury. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1 were upregulated, while granulocyte macrophage colony-stimulating factor was downregulated during EVLP (p < 0.05). IL-1β, IL-4, IL-7, IL-12, interferon-γ, macrophage inflammatory protein-1β, and tumor necrosis factor-α were detectable and unchanged.

Conclusions

Ex-vivo lung perfusion demonstrates the ability to improve oxygenation and physiologic lung function in donor lungs unacceptable for transplantation without injury to the lung. We establish here a cytokine expression profile in human lungs undergoing normothermic EVLP. These data can be used in the future to explore novel targeted therapies for ischemia-reperfusion injury.

Section snippets

Human Lung Procurement and Preparation for EVLP

Single human lungs from organ donors deemed unacceptable for transplantation after thorough evaluation for a variety of reasons, such as poor oxygenation, pulmonary contusion or consolidation, patient history of asthma, and donor-recipient size mismatch, were used for this study. A waiver for the use of these human lungs was obtained from the Colorado Multiple Institutional Review Board. Before procurement, the PaO2 was recorded with the FiO2 set at 100%. Single donor lungs were procured using

Oxygenation and Pulmonary Function Improve Significantly With EVLP

After 12 hours of EVLP, all lungs met transplant criteria for oxygenation. The PaO2 on 100% FiO2 improved significantly by more than 35% during the first 2 hours of perfusion compared with the donor's last-recorded PaO2 on 100% FiO2 (p < 0.05; Fig 1). The PVR also significantly improved at hours 7, 9, 10, 11, and 12 of EVLP compared with early perfusion (p < 0.05; Fig 2).

No Pulmonary Edema Formation During EVLP

Over the course of the 12-hour EVLP, no pulmonary edema formation was noted in the single human lung as calculated by the wet

Comment

Ex-vivo lung perfusion is emerging as a powerful method to expand the current donor pool for lung transplantation. The technique of normothermic EVLP has the ability to recondition lungs normally thought to be unacceptable for transplantation [6, 8]. This technique also provides more time to evaluate lungs outside the donor body, possibly identifying additional acceptable lungs merely by being able to monitor them under more stringent, controllable conditions than are allowed in the donor body.

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*

Both authors contributed equally.

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