Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Division of Surgical Research, University Hospital Zurich, Zurich, Switzerland.
Eur J Cardiothorac Surg. 2017 Jul 1;52(1):171-177. doi: 10.1093/ejcts/ezx053.
Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model.
Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed.
There was a trend towards better oxygenation during EVLP in the TMZ group ( P = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P < 0.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P < 0.05).
Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function.
离体肺灌注（EVLP）不仅用于评估边缘供体肺，还可用作在体外输送治疗剂的平台。我们之前在大鼠模型中证明了曲美他嗪（TMZ）对缺血再灌注（IR）损伤的有益作用。本研究评估了 TMZ 在猪 EVLP 移植模型中的作用。
猪肺在 4°C 下保存 24 小时，然后进行 4 小时 EVLP。同种异体移植物随机分为 2 组（每组 n = 5）。在 EVLP 前，TMZ（5mg/kg）加入基础液中。EVLP 后，将左肺移植，并观察受体 4 小时。整个再灌注过程中每小时记录同种异体肺的气体交换功能和肺力学。评估肺损伤的微观结构以及炎症和生化参数。
TMZ 组在 EVLP 过程中氧合趋势更好（ P = 0.06）。移植后，在 4 小时的再灌注期间以及在同种异体移植物隔离 10 分钟后，肺气体交换明显更好（ P < 0.05）。在 EVLP 结束时，TMZ 组组织硫代巴比妥酸水平、髓过氧化物酶活性和支气管肺泡灌洗液样本中的蛋白浓度显着降低（ P < 0.05）。
用 TMZ 对供体肺进行离体治疗可显著改善移植后即刻的肺功能。需要进一步的研究来了解这种策略对长期肺功能的影响。
