Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.
Ann Thorac Surg. 2011 Aug;92(2):478-84. doi: 10.1016/j.athoracsur.2011.04.027. Epub 2011 Jun 25.
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.
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.
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.
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.
供体肺短缺导致患者无法接受挽救生命的移植。体外肺灌注 (EVLP) 是一种可行的方法，可以通过评估和潜在改善供体肺功能来扩大供体池。EVLP 对人体肺组织的代谢和炎症影响目前尚不清楚。我们试图在经过长时间的常温 EVLP 后，建立符合可接受肺移植标准的人类供体肺的代表性细胞因子表达。
7 个人体单肺因各种原因不符合传统移植标准，进行常温 EVLP。用去氧胶体灌注肺，按标准方案复温并通气。每小时评估肺功能。在 1、6 和 12 小时取活检。使用基于人细胞因子磁珠的多重检测法定量测量炎症细胞因子。
所有肺在 EVLP 后均符合传统移植标准。动脉血氧分压和生理肺功能明显改善 (p<0.05)。未形成肺水肿，组织学未见急性肺损伤证据。IL-6、IL-8、粒细胞集落刺激因子和单核细胞趋化蛋白-1 在 EVLP 期间上调，而粒细胞巨噬细胞集落刺激因子下调 (p<0.05)。IL-1β、IL-4、IL-7、IL-12、干扰素-γ、巨噬细胞炎症蛋白-1β 和肿瘤坏死因子-α可检测到但不变。
EVLP 能够改善不可接受移植的供体肺的氧合和生理肺功能，而不会对肺造成损伤。我们在此建立了常温 EVLP 中人类肺的细胞因子表达谱。这些数据可用于未来探索缺血再灌注损伤的新型靶向治疗。
